Luxury Auto Growth, Finance, and Competency to Execute

Luxury Auto Growth, Finance, and Competency to Execute

The luxury athletics car or truck enterprise is booming. Automakers are now globally incentivized to develop the electrical and hybrid luxury motor vehicles the more youthful demographic requires.

Automakers designed the initially electric automobiles together with combustion engines in the early 1800s, but the 21st century has introduced a resurgence of these kinds of engines. So substantially so, that Lamborghini, the Volkswagen Group-owned sporting activities vehicle producer, has designed a 10-figure commitment to producing electrical and hybrid vehicles around the next five yrs. It strategies to launch plug-in hybrids in 2024.

Paolo Poma, CFO of Lamborghini, is on the entrance lines of the change. He and his team are modifying to the change through a confident solution, new sorts of information examination, and getting edge of all the discovering chances that crop up. Like a lot of other organizations, talent troubles are a recurring trouble for Lamborghini. As the enterprise shifts in direction of a concentrate on performance, electrification, and sustainability, it is in have to have of folks who can skillfully collect, examine, and forecast employing knowledge in these new environments. 


Paolo Poma JPG.jpgPaolo Poma 

CFO, Automobili Lamborghini 

  • Very first CFO placement: 2011
  • Notable prior providers:
    • Volkswagen Team
    • Ducati Motor Holdings
    • Tenaris
    • McKinsey & Organization

This interview has been edited for brevity and clarity.

ADAM ZAKI: When I think of Lamborghini, I consider of a loud, impressive, gasoline-guzzling sports activities motor vehicle that showcases glimpse and efficiency. What is the imagined approach driving the company’s drive for electric powered autos, and what are some of the anticipated troubles for your staff?

PAOLO POMA: This is a major challenge, not just for Lamborghini, but for our complete industry, for the reason that of what you mention, as perfectly as regulatory motives. The major challenges in our initiative are regulatory troubles, which can outcome in large penalties if not satisfied. On the other hand, we are in a good placement simply because most of our buyers are about or under 40 yrs outdated, and they are more delicate to sustainability.

Back in 2015, we attained climate neutrality in our amenities. Now, we are acquiring into the sustainability of the product, a €2.5B expenditure in 5 yrs, fully self-financed, towards electrification. By the beginning of 2025, we will be the 1st participant in our marketplace to be entirely hybridized.

Anticipations are that awesome electric autos will clearly show up in the second part of the decade, so our customers are seeking ahead to having sustainable merchandise. We are giving them these possibilities by slicing 50{49e09b23eae7466ccc7574c19ebb3019301c9a11d2999feff81a3526451546a5} of CO2 emissions by the stop of 2024 and by 80{49e09b23eae7466ccc7574c19ebb3019301c9a11d2999feff81a3526451546a5} with the introduction of electrification.

Urus.webp

The Urus will be entirely-electric by 2029. Photograph CRED: Lamborghini

What are you seeking for when deciding in which locations of the globe these sustainability efforts will be much more successful?

POMA: We are always following worldwide prosperity or richness to determine these designs. So, we comply with the concentration of the wealthy and thank God, that quantity is growing at the base of 7{49e09b23eae7466ccc7574c19ebb3019301c9a11d2999feff81a3526451546a5} compounded once-a-year development in the last 15 decades. This is our major result in. I never see significant alterations in the finances for these groups of persons.

Infrastructure availability in several areas will also drive the implementation of not only mass-market place autos but also our multipurpose, a person-of-a-variety autos.

How have the electric initiatives directly impacted you and the finance department?

POMA: On the a person hand, we have a unique prospect if we chat about the risk of electrification additional escalating our profitability. In these discussions, we are both economically smart and optimistic for the foreseeable future, due to the fact we are confident in the mixture of electrification with overall performance for our automobiles.

Internally, we will adapt our teams to the improvements, since they have to cope with the implementation of electrified products and solutions. This signifies new forms of jobs. Our groups need to have know-how of the new factors to do the job and converse with our progress engineers. They have to have to have a good knowing while getting a superior compromise in between effectiveness and price. But I see that as an prospect, not as a obstacle or risk.

electric lambo.webp

The Sián Roadster has a thoroughly hybrid V-12 powertrain with 808 HP. Image CRED: Lamborghini 

Across industries, talent challenges look to not be about the number of staff members out there, but the high quality of their skill sets. Are you enduring this, and what talent concerns are you faced with? 

POMA: You contact on the big challenge that we’re going to confront in the implementation and execution of the change to hybridization and electrification. We have been growing considerably as a firm. Lamborghini 10 decades in the past was a $200 million business. Last yr, we broke the two billion threshold [in revenue]. 

It’s not just about finances, but the competency to execute. So the expertise difficulties are brought on by a deficiency of competencies in the marketplace, making it more durable and harder to come across talent. With our quickly progress, this has been a critical trouble for us. 

We are viewing difficulties in two important spots, one particular of which is beneath my command — IT. We have to have a lot more individuals equipped to leverage new technologies. This is a thing that is again, a challenge for us, for the reason that leveraging new systems and making new use scenarios [and] new alternatives for revenue streams in the foreseeable future are incredibly important.

The second a person is solution progress. Those people teams are moving far more from mechanical challenges to electrical, technological, and digital development issues. So, we need technological people today in cybersecurity, electronics, and product progress. That signifies having an extraordinary crew of knowledge scientists that can leverage our massive collections of facts.

Getting capable to make use cases and leverage the data is obtaining seriously essential, and these forms of capabilities missing in the labor industry are starting to be much more tough to employ. To remedy this, we are operating right with several universities to explain to them the style of competencies we want from long term employees. 

What parts of the better world wide financial state will have the most influence on Lamborghini?

POMA: There are surely things that are positively impacting our organization. First, the concentration of prosperity in the earth suitable now is expanding our customer base. The 2nd aspect is the greater expending practices of substantial-web-truly worth persons following COVID, and [the] 3rd is the general power of the US greenback, specified the fact that the whole luxury small business is pretty substantially concentrated on the U.S. as the most important current market.

I really do not see the habits of prosperous people today or the concentration of their prosperity altering anytime shortly. The power of the US dollar may well reduce in the potential, and that is a prospective suffering point for us. Geopolitically, we are currently being impacted by the decoupling concerning China and the U.S., simply because the U.S. is the most important sector for us, and China is our 2nd-very best market. This will make it hard to do organization in each locations as time goes on. Further rigidity between China and the U.S. will make it much more hard to obtain our two top markets.

What profession tips would you give to anyone who desires to be a CFO of a enterprise like Lamborghini? What pieces of your occupation did you discover from the most that gave you the skills wanted to do the occupation perfectly?

POMA: I did not arrive from a conventional CFO qualifications, like from the Big 4 of accounting or a little something equivalent. I’m an engineer, and I’m coming from functions. I decided to sign up for an MBA method, which I strongly recommend to aspiring economical leaders. The MBA was substantial for me in my occupation.

I worked for McKinsey, and that was a different pretty critical move. Remaining a CFO, it is incredibly vital to be a lover in the small business, so comprehending the business as a whole is important.  I would strongly propose to colleagues or other monetary leaders that are eager to sign up for greater organizations to proceed to cherish the learning course of action.

I am attending a study course at Harvard just after this, a single working day in New York ideal up to Boston due to the fact you by no means prevent mastering. 

Dh1,000 fine, black points for illegally modified cars

Dh1,000 fine, black points for illegally modified cars

Dubai: Motorists who created unlawful modifications on their vehicles are becoming urged to ditch the increase-ons as section of a new consciousness campaign.

Altering exhaust pipes to strengthen the engine seem or modifying/turbo-charging the engine to attain greater velocity are illegal in the emirate.

The marketing campaign, introduced on Wednesday, aims to teach young drivers on the potential risks of modifying motor vehicles and then utilizing them on community roads.

Police stated that noise air pollution and stunt driving caused by this sort of vehicles have caught the consideration of the public and authorities.

Law enforcement stated they will not tolerate these conduct and will choose motion against violators.

Automobiles confiscated, owners fined

The Dubai Police Standard Command, through its Basic Department of Website traffic, seized 1,195 autos and issued fines for 4,533 autos in 2022 for unlawful motor modifications and extreme noise air pollution.

Brig. Juma Salem bin Suwaidan, Acting Director of the Basic Office of Targeted traffic, declared the figures through a push convention held at the Dubai Police Normal Headquarters.

In 2022, Dubai Law enforcement seized 1,079 motor vehicles and issued fines to 2,361 vehicles for engine modifications. In addition 116 motor vehicles were being impounded and 2,172 automobiles have been fined for excessive noise pollution.

Brig Bin Suwaidan emphasised that Dubai Law enforcement patrols are energetic throughout the emirate, focusing on curbing these poor behaviours, negatively impacting highway people, youngsters, the aged, and individuals.

250 automobiles seized in Q1 2023

Brig. Bin Suwaidan stated throughout the initial quarter of 2023, police have seized 250 vehicles and fined 327 motorists for unlawful motor modifications, and impounded 19 automobiles and fined 230 other individuals for sound pollution.

Police discussed that seizure and fines involved motorists from diverse age and unique nationalities and they ended up fully commited in different sections of Dubai.

For the duration of winter and spring months, younger individuals with the illegally modified cars are generally observed driving all around in Al Riwyah and Al Qudra.

Brig. Bin Suwaidan urged mom and dad to watch their children’s steps and educate them on the opportunity outcomes of this sort of behaviours.

He pressured the importance of family members involvement in website traffic security endeavours, working alongside the police to preserve a secure and tranquil neighborhood.

Brig. Bin Suwaidan stressed on Dubai Police’s motivation to make sure street basic safety by continually enforcing site visitors laws and conducting strategies concentrating on damaging behaviour.

The campaign will include subject visits to schools and universities and workshops for students.

Phone 901

As aspect of the push, the law enforcement would organise a series of lectures at universities, ports clubs, and other public areas, as properly as elevate recognition on different media which includes social media channels.

This Ramadan, Law enforcement groups will also visit tents in residential regions to distribute consciousness.

“Parents have a main part in seeing over their kids and not letting them to use their vehicles. Customers of the public should really help police and connect with 901 if they notice any incidents involving modified automobiles, or report it through We Are All Police Application, Brig. Suwaidan claimed.

“Modifying vehicles can trigger loss of life or injuries. This marketing campaign will target motorists who illegally modify their autos in purchase to raise their velocity. We have witnessed key targeted traffic accidents mainly because of modifying autos,” said Brig. Suwaidan.

Col. Omar Ashour, the Deputy Director of Naif Law enforcement Station mentioned modifying a motor vehicle could land the operator in difficulty. “Modifying a motor vehicle is a deadly action. It is so harmful on our roads. The owner can be fined and prosecuted in circumstance of an incident or harming home,” Brig. Suwaidan mentioned.

Numerous motorists were referred to general public prosecution and then to the court docket for authorized action.

Motor vehicle workshops monitored

Dubai police, in cooperation with financial office and its strategic partners, will monitor workshops which manufactured modifications on motor vehicle and lawful action will be taken in opposition to them.

Brig. Suaidan defined that some brand names of motor vehicles have loud audio in their manufactures, but if police catch motorist enhance the seem deliberty at signal or roundabout or other places ,then police will taken motion versus the motorist.

Brig. Suwaidan pointed out that the govt allocated sites for this sort of interest and youthful men and women are urged to visit these place as a substitute to push there.

Police have seized sizzling-rod motor vehicles utilized by younger men and women in stunt driving. In specified scenarios, law enforcement arrived throughout motor vehicles powered by aviation fuel to enhance speed.

Parent’s legal responsibility

Dubai Police stated that underage driving and illegal vehicle modification by children would be their parents’ legal responsibility.

In the celebration that mothers and fathers profess ignorance about their insignificant young children driving cars and trucks and leading to mishaps, they will be obliged to pay out compensations and blood money in scenario of casualty.

According to the Federal Targeted visitors Legislation, motorists who modify their vehicles or engine can be fined Dh1,000, and they may be slapped with 12 targeted visitors black factors. Police can confiscate the motor vehicle for 30 days for the offence.

Driving a car leading to loud sound can incur a good of Dh2,000 and 12 black factors.

If the violations repeated law enforcement will double the fines and it may be achieved to Dh100,000

3 local police departments join national car repair voucher program

3 local police departments join national car repair voucher program

CHULA VISTA, Calif. (KGTV) – You can be hitting the road for perform, college, grocery retailer, you identify it.

Sometimes you may perhaps not know that your headlights, taillights or transform indicators could be out which can direct to one thing like having pulled around and ticketed.

 “We do not want some getting these prospects due to the fact they just cannot manage it now to just just take that risk and get on the road when they can just get it fixed,” reported Sgt. Anthony Molina with the Chula Vista Law enforcement Office.

But that can improve in the coming months many thanks to a system named Lights On!.

“So, they are likely to get a voucher and what it is superior for is up to $250 for the repair service,” reported Molina. “These are people options for our officers to have interaction with them in a quite distinct way than they are made use of to.”

The program’s mission is to change the tickets to take care of burnt out lights presented to all those motorists with mend vouchers which was made by a Minneapolis-based nonprofit MicroGrants.

Chula Vista law enforcement data exhibit that 1,821 of these kinds of citations have been issued from 2019 to 2023 year to day.

Chula Vista, National City and San Diego Police Departments are the 1st businesses in California to just take part in it. San Diego Police said in a push launch the departments have partnered with the San Diego Padres Foundation, and Scripps Health to fund the initiative and all donations are matched by MicroGrants.

“This is now a further resource that our officers have. So, when they have all those times of this is the correct software to use, they can use it,” Molina reported. “Instead of causing a downward spiral possibly be a part of that lifting up.”

And lifting up the local community is a thing some people can help.

“Sometimes men and women can afford it and that most likely provides on to an additional invoice, so I feel that is a genuinely excellent factor,” Naniece Gonalez reported.

“Usually if somebody’s headlight is out most of the time, they’re experiencing some type of monetary hardship. And, you know, a person ticket can lead to far more and them getting rid of their license,” Eileen Penders mentioned.

As Chula Vista Police and other businesses goal to use this to make roads safer with the about three-yr system, they are also making absolutely sure know that rules and insurance policies are not modifying.

“Some of the big things we’re producing confident that individuals understand is that it’s an solution it is not an each time matter. We’re hopeful all over again it will become a way to bridge that gap concerning the local community and our law enforcement department. And it is not just in this article in Chula Vista but in our County,” reported Molina.

San Diego Police claimed officers are even now equipped act on other violations that might be present at the time of the website traffic quit. Chula Vista Police advised ABC 10Information they’ve gotten 4 auto retailers to take part in the repair voucher program.

Safelite Auto Glass Review: Services And Cost (2023)

Safelite Auto Glass Review: Services And Cost (2023)

Vehicle Glass Provider Cost Elements

As you can see from the quote table above, the rate of auto glass providers may differ for even the identical careers. That’s simply because there are several vital elements that enable to figure out the cost of glass repairs and replacements. These elements contain the adhering to:

  • Form of car or truck: Your car’s yr, make, design, and even trim degree figure out the alternative glass required to full the job. In normal, glass replacements for luxury cars and other costly motor vehicles charge much more than individuals for a lot more widespread autos.
  • Kind of injury: Lesser chips and cracks can be repaired, although other people have to have an high-priced substitution. The style of damage can also adjust how difficult it is to take away damaged glass, which influences the job’s charge.
  • Windshield know-how: Windshields that include ADAS and other basic safety characteristics cost significantly far more to substitute. They also are likely to involve calibration, which is a support that comes with an additional rate.
  • Replacement glass variety: Some businesses use substitute glass produced by the original gear producer (OEM). This glass, which is usually offered at dealerships, is built to the exact requirements of the component it is changing but costs significantly a lot more than aftermarket glass.
  • Your location: Sector prices for automobile glass companies in your place and other local elements impact the quantity you are going to spend.
  • Spot of damage: Alternative glass for diverse panels may differ in charge. A new windshield, for example, may charge more than rear glass depending on your car.

Safelite Bargains

On its site, Safelite presently gives two discount coupons for discount rates on car glass providers:

  • $45 off windshield alternative
  • $15 off windshield mend

To use these bargains, you must e-book your services by means of Safelite.com and use the codes presented. These reductions cannot be made use of for fleet services or put together with employment included less than a motor vehicle coverage assert.

Does Car or truck Insurance policies Go over Broken Glass?

Car insurance policy will choose treatment of damaged glass repairs or replacements, but only if you have the proper protection strategy. To acquire payments for auto glass services, you’ll have to have a “comprehensive coverage” coverage that features collision and extensive insurance coverage.

  • Collision coverage: Handles auto glass problems ensuing from a vehicle incident regardless of who brought on it
  • Extensive coverage: Covers window and windshield destruction from nonaccident sources such as vehicle theft, vandalism, and severe weather conditions such as flooding or hail

Your car coverage card must list out the protections on your coverage. If you never have entire coverage, it is truly worth talking to an agent to see how introducing them could affect your rates. Insurance plan gurus endorse full protection in most situations if motorists can find the money for it.

How To Use Car Insurance With Safelite

If you pick out to function with an coverage organization, Safelite can submit a assert to your insurance provider. To get the procedure begun on line, just suggest your provider, enter your plan amount, and deliver info on how the problems happened. Safelite will validate your protection and then you can schedule an appointment.

Considering the fact that there are a several ways involved, Safelite allows you help you save your progress and arrive back later by entering a telephone selection or e mail address.

Which States Have Free Windshield Alternative?

Florida, Kentucky, and South Carolina drivers receive no cost windshield replacements if they have complete coverage. This means that people in require of vehicle glass solutions who at the moment have detailed insurance will get a totally free, zero-deductible windshield replacement.

In some states, you can get independent zero-deductible glass protection. These states incorporate:

  • Arizona
  • Connecticut
  • Massachusetts
  • Minnesota
  • New York

In other states, drivers will ordinarily have to spend a automobile insurance plan deductible prior to collision or in depth protection kicks in.

Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility | Journal of Translational Medicine

Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility | Journal of Translational Medicine
  • Cartellieri M, Feldmann A, Koristka S, Arndt C, Loff S, Ehninger A, et al. Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts. Blood Cancer J. 2016;6(8):e458.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Frigault MJ, Lee J, Basil MC, Carpenito C, Motohashi S, Scholler J, et al. Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells. Cancer Immunol Res. 2015;3(4):356–67.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cruz CR, Hanley PJ, Liu H, Torrano V, Lin YF, Arce JA, et al. Adverse events following infusion of T cells for adoptive immunotherapy: a 10-year experience. Cytotherapy. 2010;12(6):743–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010;18(4):843–51.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ramos CA, Savoldo B, Dotti G. CD19-CAR trials. Cancer J. 2014;20(2):112–8.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gross G, Eshhar Z. Therapeutic potential of T cell chimeric antigen receptors (CARs) in cancer treatment: counteracting off-tumor toxicities for safe CAR T cell therapy. Annu Rev Pharmacol Toxicol. 2016;56:59–83.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fisher J, Abramowski P, Wisidagamage Don ND, Flutter B, Capsomidis A, Cheung GW, et al. Avoidance of on-target off-tumor activation using a co-stimulation-only chimeric antigen receptor. Mol Ther. 2017;25(5):1234–47.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hay KA, Hanafi LA, Li D, Gust J, Liles WC, Wurfel MM, et al. Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood. 2017;130(21):2295–306.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47–62.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tokarew N, Ogonek J, Endres S, von Bergwelt-Baildon M, Kobold S. Teaching an old dog new tricks: next-generation CAR T cells. Br J Cancer. 2019;120(1):26–37.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sharma N, Reagan PM, Liesveld JL. Cytopenia after CAR-T cell therapy—a brief review of a complex problem. Cancers. 2022;14(6):1501.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wallet F, Sesques P, Devic P, Levrard M, Ader F, Friggeri A, et al. CAR-T cell: toxicities issues: mechanisms and clinical management. Bull Cancer. 2021;108(10S):S117-27.

    Article 
    PubMed 

    Google Scholar
     

  • Zhang K, Chen H, Li F, Huang S, Chen F, Li Y. Bright future or blind alley? CAR-T cell therapy for solid tumors. 2023. https://www.genome.jp/kegg/. Accessed 28 Feb 2023.

  • Yu S, Yi M, Qin S, Wu K. Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. Mol Cancer. 2019;18(1):125.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Andrea AE, Chiron A, Bessoles S, Hacein-Bey-Abina S. Engineering next-generation CAR-T cells for better toxicity management. Int J Mol Sci. 2020;21(22):8620.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mao R, Kong W, He Y. The affinity of antigen-binding domain on the antitumor efficacy of CAR T cells: moderate is better. Front Immunol. 2022;13:1032403.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu Y, Huang Z, Harrison R, Liu L, Zhu L, Situ Y, Wang Y. Engineering CAR T cells for enhanced efficacy and safety. APL Bioeng. 2022;6:11502. https://doi.org/10.1063/5.0073746.

    Article 
    CAS 

    Google Scholar
     

  • Madderson O, Teixeira AP, Fussenegger M. Emerging mammalian gene switches for controlling implantable cell therapies. Curr Opin Chem Biol. 2021;1(64):98–105.

    Article 

    Google Scholar
     

  • Feldmann A, Arndt C, Koristka S, Berndt N, Bergmann R, Bachmann MP. Conventional CARs versus modular CARs. Cancer Immunol Immunother. 2019;68(10):1713–9.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arndt C, Fasslrinner F, Loureiro LR, Koristka S, Feldmann A, Bachmann M. Adaptor CAR platforms-next generation of T cell-based cancer immunotherapy. Cancers. 2020;12(5):1302.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu D, Zhao J, Song Y. Engineering switchable and programmable universal CARs for CAR T therapy. J Hematol Oncol. 2019;12(1):69.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sutherland AR, Owens MN, Geyer CR. Modular chimeric antigen receptor systems for universal CAR T cell retargeting. Int J Mol Sci. 2020;21(19):7222.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gamboa L, Zamat AH, Kwong GA. Synthetic immunity by remote control. Theranostics. 2020;10(8):3652–67.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zheng Y, Nandakumar KS, Cheng K. Optimization of CAR-T cell-based therapies using small-molecule-based safety switches. J Med Chem. 2021;64(14):9577–91.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Miao L, Zhang J, Huang B, Zhang Z, Wang S, Tang F, et al. Special chimeric antigen receptor (CAR) modifications of T cells: a review. Front Oncol. 2022;12:832765.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016;127(26):3321–30.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sahillioglu AC, Schumacher TN. Safety switches for adoptive cell therapy. Curr Opin Immunol. 2022;74:190–8.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Caliendo F, Dukhinova M, Siciliano V. Engineered cell-based therapeutics: synthetic biology meets immunology. Front Bioeng Biotechnol. 2019;7:43.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • van Schandevyl S, Kerre T. Chimeric antigen receptor T-cell therapy: design improvements and therapeutic strategies in cancer treatment. Acta Clin Belg. 2020;75(1):26–32.

    Article 
    PubMed 

    Google Scholar
     

  • Heard A, Chang J, Warrington JM, Singh N. Advances in CAR design. Best Pract Res Clin Haematol. 2021;34(3):101304.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zajc CU, Salzer B, Taft JM, Reddy ST, Lehner M, Traxlmayr MW. Driving CARs with alternative navigation tools—the potential of engineered binding scaffolds. FEBS J. 2021;288(7):2103–18.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tahmasebi S, Elahi R, Khosh E, Esmaeilzadeh A. Programmable and multi-targeted CARs: a new breakthrough in cancer CAR-T cell therapy. Clin Transl Oncol. 2021;23(6):1003–19.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mi J, Ye Q, Min Y. Advances in nanotechnology development to overcome current roadblocks in CAR-T therapy for solid tumors. Front Immunol. 2022;13:849759.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Safarzadeh Kozani P, Naseri A, Mirarefin SMJ, Salem F, Nikbakht M, Evazi Bakhshi S, et al. Nanobody-based CAR-T cells for cancer immunotherapy. Biomark Res. 2022;10(1):24.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kyte JA. Strategies for improving the efficacy of CAR T cells in solid cancers. Cancers. 2022;14(3):571.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schaft N. The landscape of CAR-T cell clinical trials against solid tumors—a comprehensive overview. Cancers. 2020;12(9):2567.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Karlsson H, Svensson E, Gigg C, Jarvius M, Olsson-Stromberg U, Savoldo B, et al. Evaluation of intracellular signaling downstream chimeric antigen receptors. PLoS ONE. 2015;10(12):e0144787.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sadelain M, Riviere I, Riddell S. Therapeutic T cell engineering. Nature. 2017;545(7655):423–31.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brenner MJ, Cho JH, Wong NML, Wong WW. Synthetic biology: immunotherapy by design. Annu Rev Biomed Eng. 2018;20:95–118.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379(1):64–73.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • MacKay M, Afshinnekoo E, Rub J, Hassan C, Khunte M, Baskaran N, et al. The therapeutic landscape for cells engineered with chimeric antigen receptors. Nat Biotechnol. 2020;38(2):233–44.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Park CH. Making potent CAR T cells using genetic engineering and synergistic agents. Cancers. 2021;13(13):3236.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chuang ST, Conklin B, Stein JB, Pan G, Lee KB. Nanotechnology-enabled immunoengineering approaches to advance therapeutic applications. Nano Convergence. 2022;9(1):1–31. https://doi.org/10.1186/s40580-022-00310-0.

    Article 
    CAS 

    Google Scholar
     

  • Jones BS, Lamb LS, Goldman F, di Stasi A. Improving the safety of cell therapy products by suicide gene transfer. Front Pharmacol. 2014;5:254.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tey SK. Adoptive T-cell therapy: adverse events and safety switches. Clin Transl Immunol. 2014;3(6):e17.

    Article 

    Google Scholar
     

  • Resetca D, Neschadim A, Medin JA. Engineering hematopoietic cells for cancer immunotherapy: strategies to address safety and toxicity concerns. J Immunother. 2016;39(7):249–59.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Straathof KC, Pule MA, Yotnda P, Dotti G, Vanin EF, Brenner MK, et al. An inducible caspase 9 safety switch for T-cell therapy. Blood. 2005;105(11):4247–54.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Berger C, Flowers ME, Warren EH, Riddell SR. Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation. Blood. 2006;107(6):2294–302.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, et al. Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell. 1998;94(3):339–52.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tiberghien P. Use of suicide genes in gene therapy. J Leukoc Biol. 1994;56(2):203–9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Beltinger C, Fulda S, Kammertoens T, Meyer E, Uckert W, Debatin KM. Herpes simplex virus thymidine kinase/ganciclovir-induced apoptosis involves ligand-independent death receptor aggregation and activation of caspases. Proc Natl Acad Sci USA. 1999;96(15):8699–704.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Spencer DM, Belshaw PJ, Chen L, Ho SN, Randazzo F, Crabtree GR, et al. Functional analysis of Fas signaling in vivo using synthetic inducers of dimerization. Curr Biol. 1996;6(7):839–47.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Introna M, Barbui AM, Bambacioni F, Casati C, Gaipa G, Borleri G, et al. Genetic modification of human T cells with CD20: a strategy to purify and lyse transduced cells with anti-CD20 antibodies. Hum Gene Ther. 2000;11(4):611–20.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kao RL, Truscott LC, Chiou TT, Tsai W, Wu AM, de Oliveira SN. A cetuximab-mediated suicide system in chimeric antigen receptor-modified hematopoietic stem cells for cancer therapy. Hum Gene Ther. 2019;30(4):413–28.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang Q, He F, He W, Huang Y, Zeng J, Zi F, et al. A transgene-encoded truncated human epidermal growth factor receptor for depletion of anti- B-cell maturation antigen CAR-T cells. Cell Immunol. 2021;363:104342.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Freytag SO, Khil M, Stricker H, Peabody J, Menon M, DePeralta-Venturina M, et al. Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res. 2002;62(17):4968–76.

    CAS 
    PubMed 

    Google Scholar
     

  • Tone Y, Kawahara M, Kawaguchi D, Ueda H, Nagamune T. Death signalobody: inducing conditional cell death in response to a specific antigen. Hum Gene Ther Methods. 2013;24(3):141–50.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wiebking V, Patterson JO, Martin R, Chanda MK, Lee CM, Srifa W, et al. Metabolic engineering generates a transgene-free safety switch for cell therapy. Nat Biotechnol. 2020;38(12):1441–50.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wu X, Shi B, Zhang J, Shi Z, Di S, Fan M, et al. A fusion receptor as a safety switch, detection, and purification biomarker for adoptive transferred T cells. Mol Ther. 2017;25(10):2270–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shaw T, Quan J, Totoritis MC. B cell therapy for rheumatoid arthritis: the rituximab (anti-CD20) experience. Ann Rheum Dis. 2003;62(Suppl 2):ii55-9.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Putyrski M, Schultz C. Protein translocation as a tool: the current rapamycin story. FEBS Lett. 2012;586(15):2097–105.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bonini C, Bordignon C. Potential and limitations of HSV-TK-transduced donor peripheral blood lymphocytes after allo-BMT. Hematol Cell Ther. 1997;39(5):273–4.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tiberghien P. Use of suicide gene-expressing donor T-cells to control alloreactivity after haematopoietic stem cell transplantation. J Intern Med. 2001;249(4):369–77.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ciceri F, Bonini C, Stanghellini MT, Bondanza A, Traversari C, Salomoni M, et al. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncol. 2009;10(5):489–500.

    Article 
    PubMed 

    Google Scholar
     

  • Traversari C, Marktel S, Magnani Z, Mangia P, Russo V, Ciceri F, et al. The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies. Blood. 2007;109(11):4708–15.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Casucci M, di Nicolis Robilant B, Falcone L, Camisa B, Norelli M, Genovese P, et al. CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood. 2013;122(20):3461–72.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Riddell SR, Elliott M, Lewinsohn DA, Gilbert MJ, Wilson L, Manley SA, et al. T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nat Med. 1996;2(2):216–23.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lupo-Stanghellini MT, Provasi E, Bondanza A, Ciceri F, Bordignon C, Bonini C. Clinical impact of suicide gene therapy in allogeneic hematopoietic stem cell transplantation. Hum Gene Ther. 2010;21(3):241–50.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Preuss E, Muik A, Weber K, Otte J, von Laer D, Fehse B. Cancer suicide gene therapy with TK.007: superior killing efficiency and bystander effect. J Mol Med. 2011;89(11):1113–24.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997;91(4):479–89.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Duong MT, Collinson-Pautz MR, Morschl E, Lu A, Szymanski SP, Zhang M, et al. Two-dimensional regulation of CAR-T cell therapy with orthogonal switches. Mol Ther Oncolytics. 2019;12:124–37.

    Article 
    PubMed 

    Google Scholar
     

  • Lu YJ, Chu H, Wheeler LW, Nelson M, Westrick E, Matthaei JF, et al. Preclinical evaluation of bispecific adaptor molecule controlled folate receptor CAR-T cell therapy with special focus on pediatric malignancies. Front Oncol. 2019;9:151.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lipus A, Janosz E, Ackermann M, Hetzel M, Dahlke J, Buchegger T, et al. Targeted integration of inducible caspase-9 in Human iPSCs allows efficient in vitro clearance of iPSCs and iPSC-macrophages. Int J Mol Sci. 2020;21(7):2481.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Quintarelli C, Vera JF, Savoldo B, Giordano Attianese GM, Pule M, Foster AE, et al. Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes. Blood. 2007;110(8):2793–802.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • de Witte MA, Jorritsma A, Swart E, Straathof KC, de Punder K, Haanen JB, et al. An inducible caspase 9 safety switch can halt cell therapy-induced autoimmune disease. J Immunol. 2008;180(9):6365–73.

    Article 
    PubMed 

    Google Scholar
     

  • Diaconu I, Ballard B, Zhang M, Chen Y, West J, Dotti G, et al. Inducible caspase-9 selectively modulates the toxicities of CD19-specific chimeric antigen receptor-modified T cells. Mol Ther. 2017;25(3):580–92.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hoyos V, Savoldo B, Quintarelli C, Mahendravada A, Zhang M, Vera J, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia. 2010;24(6):1160–70.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365(18):1673–83.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Budde LE, Berger C, Lin Y, Wang J, Lin X, Frayo SE, et al. Combining a CD20 chimeric antigen receptor and an inducible caspase 9 suicide switch to improve the efficacy and safety of T cell adoptive immunotherapy for lymphoma. PLoS ONE. 2013;8(12):e82742.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou X, Dotti G, Krance RA, Martinez CA, Naik S, Kamble RT, et al. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood. 2015;125(26):4103–13.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gargett T, Brown MP. The inducible caspase-9 suicide gene system as a “safety switch” to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells. Front Pharmacol. 2014;5:235.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fan L, Freeman KW, Khan T, Pham E, Spencer DM. Improved artificial death switches based on caspases and FADD. Hum Gene Ther. 1999;10(14):2273–85.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Thomis DC, Marktel S, Bonini C, Traversari C, Gilman M, Bordignon C, et al. A Fas-based suicide switch in human T cells for the treatment of graft-versus-host disease. Blood. 2001;97(5):1249–57.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Junker K, Koehl U, Zimmerman S, Stein S, Schwabe D, Klingebiel T, et al. Kinetics of cell death in T lymphocytes genetically modified with two novel suicide fusion genes. Gene Ther. 2003;10(14):1189–97.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Berger C, Blau CA, Huang ML, Iuliucci JD, Dalgarno DC, Gaschet J, et al. Pharmacologically regulated Fas-mediated death of adoptively transferred T cells in a nonhuman primate model. Blood. 2004;103(4):1261–9.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K, Flutter B, et al. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood. 2014;124(8):1277–87.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Valton J, Guyot V, Boldajipour B, Sommer C, Pertel T, Juillerat A, et al. A versatile safeguard for chimeric antigen receptor T-cell immunotherapies. Sci Rep. 2018;8(1):8972.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mosti L, Langner LM, Chmielewski KO, Arbuthnot P, Alzubi J, Cathomen T. Targeted multi-epitope switching enables straightforward positive/negative selection of CAR T cells. Gene Ther. 2021;28(9):602–12.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huber BE, Austin EA, Richards CA, Davis ST, Good SS. Metabolism of 5-fluorocytosine to 5-fluorouracil in human colorectal tumor cells transduced with the cytosine deaminase gene: significant antitumor effects when only a small percentage of tumor cells express cytosine deaminase. Proc Natl Acad Sci USA. 1994;91(17):8302–6.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Trinh QT, Austin EA, Murray DM, Knick VC, Huber BE. Enzyme/prodrug gene therapy: comparison of cytosine deaminase/5-fluorocytosine versus thymidine kinase/ganciclovir enzyme/prodrug systems in a human colorectal carcinoma cell line. Cancer Res. 1995;55(21):4808–12.

    CAS 
    PubMed 

    Google Scholar
     

  • Hoganson DK, Batra RK, Olsen JC, Boucher RC. Comparison of the effects of three different toxin genes and their levels of expression on cell growth and bystander effect in lung adenocarcinoma. Cancer Res. 1996;56(6):1315–23.

    CAS 
    PubMed 

    Google Scholar
     

  • Kuriyama S, Masui K, Sakamoto T, Nakatani T, Kikukawa M, Tsujinoue H, et al. Bystander effect caused by cytosine deaminase gene and 5-fluorocytosine in vitro is substantially mediated by generated 5-fluorouracil. Anticancer Res. 1998;18(5A):3399–406.

    CAS 
    PubMed 

    Google Scholar
     

  • Sakemura R, Terakura S, Watanabe K, Julamanee J, Takagi E, Miyao K, et al. A tet-on inducible system for controlling CD19-chimeric antigen receptor expression upon drug administration. Cancer Immunol Res. 2016;4(8):658–68.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gu X, He D, Li C, Wang H, Yang G. Development of inducible CD19-CAR T cells with a tet-on system for controlled activity and enhanced clinical safety. Int J Mol Sci. 2018;19(11):3455.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Drent E, Poels R, Mulders MJ, van de Donk N, Themeli M, Lokhorst HM, et al. Feasibility of controlling CD38-CAR T cell activity with a Tet-on inducible CAR design. PLoS ONE. 2018;13(5):e0197349.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ali Hosseini Rad SM, Poudel A, Tan GMY, McLellan AD. Optimisation of tet-on inducible systems for sleeping beauty-based chimeric antigen receptor (CAR) applications. Sci Rep. 2020;10(1):13125.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ramirez-Garza SL, Laveriano-Santos EP, Marhuenda-Munoz M, Storniolo CE, Tresserra-Rimbau A, Vallverdu-Queralt A, et al. Health effects of resveratrol: results from human intervention trials. Nutrients. 2018;10(12):1892.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang L, Yin J, Wu J, Qiao L, Zhao EM, Cai F, et al. Engineering genetic devices for in vivo control of therapeutic T cell activity triggered by the dietary molecule resveratrol. Proc Natl Acad Sci USA. 2021;118(34):e2106612118.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kotter B, Engert F, Krueger W, Roy A, Rawashdeh WA, Cordes N, et al. Titratable pharmacological regulation of CAR T cells using zinc finger-based transcription factors. Cancers. 2021;13(19):4741.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Niopek D, Benzinger D, Roensch J, Draebing T, Wehler P, Eils R, et al. Engineering light-inducible nuclear localization signals for precise spatiotemporal control of protein dynamics in living cells. Nat Commun. 2014;5:4404.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Taslimi A, Zoltowski B, Miranda JG, Pathak GP, Hughes RM, Tucker CL. Optimized second-generation CRY2-CIB dimerizers and photoactivatable Cre recombinase. Nat Chem Biol. 2016;12(6):425–30.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang Z, Wu Y, Allen ME, Pan Y, Kyriakakis P, Lu S, et al. Engineering light-controllable CAR T cells for cancer immunotherapy. Sci Adv. 2020;6(8):eaay9209.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pan Y, Yoon S, Sun J, Huang Z, Lee C, Allen M, et al. Mechanogenetics for the remote and noninvasive control of cancer immunotherapy. Proc Natl Acad Sci USA. 2018;115(5):992–7.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Miller IC, Zamat A, Sun LK, Phuengkham H, Harris AM, Gamboa L, et al. Enhanced intratumoural activity of CAR T cells engineered to produce immunomodulators under photothermal control. Nat Biomed Eng. 2021. https://doi.org/10.1038/s41551-021-00781-2.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu Y, Liu Y, Huang Z, Wang X, Jin Z, Li J, et al. Control of the activity of CAR-T cells within tumours via focused ultrasound. Nat Biomed Eng. 2021. https://doi.org/10.1038/s41551-021-00779-w.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Juillerat A, Marechal A, Filhol JM, Valogne Y, Valton J, Duclert A, et al. An oxygen sensitive self-decision making engineered CAR T-cell. Sci Rep. 2017;7:39833.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Prinzing B, Krenciute G. Hypoxia-inducible CAR expression: an answer to the on-target/off-tumor dilemma? Cell Rep Med. 2021;2(4):100244.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liao Q, He H, Mao Y, Ding X, Zhang X, Xu J. Engineering T cells with hypoxia-inducible chimeric antigen receptor (HiCAR) for selective tumor killing. Biomark Res. 2020;8(1):56.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kosti P, Opzoomer JW, Larios-Martinez KI, Henley-Smith R, Scudamore CL, Okesola M, et al. Hypoxia-sensing CAR T cells provide safety and efficacy in treating solid tumors. Cell Rep Med. 2021;2(4):100227.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang Z-J, Yu Z-Y, Cai Y-M, Du R-R, Cai L. Engineering of an enhanced synthetic Notch receptor by reducing ligand-independent activation. Commun Biol. 2020;3(1):116.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Morsut L, Roybal KT, Xiong X, Gordley RM, Coyle SM, Thomson M, et al. Engineering customized cell sensing and response behaviors using synthetic notch receptors. Cell. 2016;164(4):780–91.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Roybal KT, Rupp LJ, Morsut L, Walker WJ, McNally KA, Park JS, et al. Precision tumor recognition by T cells with combinatorial antigen-sensing circuits. Cell. 2016;164(4):770–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen LC, Hou AJ, Chen YY. Getting better mileage with logically primed CARs. Med. 2021;2(7):785–7.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Srivastava S, Salter AI, Liggitt D, Yechan-Gunja S, Sarvothama M, Cooper K, et al. Logic-gated ROR1 chimeric antigen receptor expression rescues T cell-mediated toxicity to normal tissues and enables selective tumor targeting. Cancer Cell. 2019;35(3):489-503.e8.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moghimi B, Muthugounder S, Jambon S, Tibbetts R, Hung L, Bassiri H, et al. Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma. Nat Commun. 2021;12(1):511.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Choe JH, Watchmaker PB, Simic MS, Gilbert RD, Li AW, Krasnow NA, et al. SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma. www.humanproteomemap.org. Accessed 7 Feb 2023.

  • Hyrenius-Wittsten A, Su Y, Park M, Garcia JM, Alavi J, Perry N, et al. SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models. Sci Transl Med. 2021;13(591):eabd8836.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Juillerat A, Tkach D, Busser BW, Temburni S, Valton J, Duclert A, et al. Modulation of chimeric antigen receptor surface expression by a small molecule switch. BMC Biotechnol. 2019;19(1):44.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cao YJ, Wang X, Wang Z, Zhao L, Li S, Zhang Z, et al. Switchable CAR-T cells outperformed traditional antibody-redirected therapeutics targeting breast cancers. ACS Synth Biol. 2021;10(5):1176–83.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Carbonneau S, Sharma S, Peng L, Rajan V, Hainzl D, Henault M, et al. An IMiD-inducible degron provides reversible regulation for chimeric antigen receptor expression and activity. Cell Chem Biol. 2021;28(6):802-812.e6.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jan M, Scarfo I, Larson RC, Walker A, Schmidts A, Guirguis AA, et al. Reversible ON- and OFF-switch chimeric antigen receptors controlled by lenalidomide. Sci Transl Med. 2021;13(575):eabb6295.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sievers QL, Gasser JA, Cowley GS, Fischer ES, Ebert BL. Genome-wide screen identifies cullin-RING ligase machinery required for lenalidomide-dependent CRL4(CRBN) activity. Blood. 2018;132(12):1293–303.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee SM, Kang CH, Choi SU, Kim Y, Hwang JY, Jeong HG, et al. A chemical switch system to modulate chimeric antigen receptor T cell activity through proteolysis-targeting chimaera technology. ACS Synth Biol. 2020;9(5):987–92.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wu CY, Roybal KT, Puchner EM, Onuffer J, Lim WA. Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Science. 2015;350(6258):aab4077.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Leung WH, Gay J, Martin U, Garrett TE, Horton HM, Certo MT, et al. Sensitive and adaptable pharmacological control of CAR T cells through extracellular receptor dimerization. JCI Insight. 2019;5:e124430.

    Article 
    PubMed 

    Google Scholar
     

  • Zajc CU, Dobersberger M, Schaffner I, Mlynek G, Puhringer D, Salzer B, et al. A conformation-specific ON-switch for controlling CAR T cells with an orally available drug. Proc Natl Acad Sci USA. 2020;117(26):14926–35.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Salzer B, Schueller CM, Zajc CU, Peters T, Schoeber MA, Kovacic B, et al. Engineering AvidCARs for combinatorial antigen recognition and reversible control of CAR function. Nat Commun. 2020;11(1):4166.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Juillerat A, Marechal A, Filhol JM, Valton J, Duclert A, Poirot L, et al. Design of chimeric antigen receptors with integrated controllable transient functions. Sci Rep. 2016;6:18950.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nguyen N, Huang K, Zeng H, Jing J, Wang R, Fang S, et al. Nano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety. Nat Nanotechnol. 2021;16:1–11.

    Article 

    Google Scholar
     

  • Sahillioglu AC, Toebes M, Apriamashvili G, Gomez R, Schumacher TN. CRASH-IT switch enables reversible and dose-dependent control of TCR and CAR T-cell function. Cancer Immunol Res. 2021;9(9):999–1007.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Giordano-Attianese G, Gainza P, Gray-Gaillard E, Cribioli E, Shui S, Kim S, et al. A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy. Nat Biotechnol. 2020;38(4):426–32.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hotblack A, Kokalaki EK, Palton MJ, Cheung GW, Williams IP, Manzoor S, et al. Tunable control of CAR T cell activity through tetracycline mediated disruption of protein-protein interaction. Sci Rep. 2021;11(1):21902.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Park S, Pascua E, Lindquist KC, Kimberlin C, Deng X, Mak YSL, et al. Direct control of CAR T cells through small molecule-regulated antibodies. Nat Commun. 2021;12(1):710.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fedorov VD, Themeli M, Sadelain M. PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci Transl Med. 2013;5(215):215ra172.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hamburger AE, DiAndreth B, Cui J, Daris ME, Munguia ML, Deshmukh K, et al. Engineered T cells directed at tumors with defined allelic loss. Mol Immunol. 2020;128:298–310.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hwang MS, Mog BJ, Douglass J, Pearlman AH, Hsiue EH, Paul S, et al. Targeting loss of heterozygosity for cancer-specific immunotherapy. Proc Natl Acad Sci USA. 2021;118(12):e2022410118.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tao L, Farooq MA, Gao Y, Zhang L, Niu C, Ajmal I, et al. CD19-CAR-T cells bearing a KIR/PD-1-based inhibitory CAR eradicate CD19(+)HLA-C1(-) malignant B cells while sparing CD19(+)HLA-C1(+) healthy B cells. Cancers. 2020. https://doi.org/10.3390/cancers12092612.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fei F, Rong L, Jiang N, Wayne AS, Xie J. Targeting HLA-DR loss in hematologic malignancies with an inhibitory chimeric antigen receptor. Mol Ther. 2021. https://doi.org/10.1016/j.ymthe.2021.11.013.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Richards RM, Zhao F, Freitas KA, Parker KR, Xu P, Fan A, et al. NOT-gated CD93 CAR T cells effectively target aml with minimized endothelial cross-reactivity. Blood Cancer Discov. 2021;2(6):648–65.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aoyama S, Yasuda S, Watanabe D, Akiyama H, Umezawa Y, Nogami A, et al. A novel protease-mediated chimeric antigen receptor (CAR): “Double-Arm” CAR-T cell system improves target specificity of CAR-T cell therapy. Blood. 2019;134(Supplement_1):1941. https://doi.org/10.1182/blood-2019-121973.

    Article 

    Google Scholar
     

  • Clemenceau B, Congy-Jolivet N, Gallot G, Vivien R, Gaschet J, Thibault G, et al. Antibody-dependent cellular cytotoxicity (ADCC) is mediated by genetically modified antigen-specific human T lymphocytes. Blood. 2006;107(12):4669–77.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kudo K, Imai C, Lorenzini P, Kamiya T, Kono K, Davidoff AM, et al. T lymphocytes expressing a CD16 signaling receptor exert antibody-dependent cancer cell killing. Cancer Res. 2014;74(1):93–103.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ochi F, Fujiwara H, Tanimoto K, Asai H, Miyazaki Y, Okamoto S, et al. Gene-modified human alpha/beta-T cells expressing a chimeric CD16-CD3zeta receptor as adoptively transferable effector cells for anticancer monoclonal antibody therapy. Cancer Immunol Res. 2014;2(3):249–62.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • D’Aloia MM, Caratelli S, Palumbo C, Battella S, Arriga R, Lauro D, et al. T lymphocytes engineered to express a CD16-chimeric antigen receptor redirect T-cell immune responses against immunoglobulin G-opsonized target cells. Cytotherapy. 2016;18(2):278–90.

    Article 
    PubMed 

    Google Scholar
     

  • Tamada K, Geng D, Sakoda Y, Bansal N, Srivastava R, Li Z, et al. Redirecting gene-modified T cells toward various cancer types using tagged antibodies. Clin Cancer Res. 2012;18(23):6436–45.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim MS, Ma JS, Yun H, Cao Y, Kim JY, Chi V, et al. Redirection of genetically engineered CAR-T cells using bifunctional small molecules. J Am Chem Soc. 2015;137(8):2832–5.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cao Y, Rodgers DT, Du J, Ahmad I, Hampton EN, Ma JS, et al. Design of switchable chimeric antigen receptor T cells targeting breast cancer. Angew Chem Int Ed Engl. 2016;55(26):7520–4.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ma JS, Kim JY, Kazane SA, Choi SH, Yun HY, Kim MS, et al. Versatile strategy for controlling the specificity and activity of engineered T cells. Proc Natl Acad Sci USA. 2016;113(4):E450-8.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang B, Wang Y, Huang S, Sun J, Wang M, Ma W, et al. Photoswitchable CAR-T cell function in vitro and in vivo via a cleavable mediator. Cell Chem Biol. 2021;28(1):60-69.e7.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kobayashi A, Nobili A, Neier SC, Sadiki A, Distel R, Zhou ZS, et al. Light-controllable binary switch activation of CAR T cells. ChemMedChem. 2022;17:e202100722.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Urbanska K, Powell DJ. Development of a novel universal immune receptor for antigen targeting: to Infinity and beyond. Oncoimmunology. 2012;1(5):777–9.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Urbanska K, Lanitis E, Poussin M, Lynn RC, Gavin BP, Kelderman S, et al. A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer Res. 2012;72(7):1844–52.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lohmueller JJ, Ham JD, Kvorjak M, Finn OJ. mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting. Oncoimmunology. 2017;7(1):e1368604.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dale GL, Gaddy P, Pikul FJ. Antibodies against biotinylated proteins are present in normal human serum. J Lab Clin Med. 1994;123(3):365–71.

    CAS 
    PubMed 

    Google Scholar
     

  • Grote S, Mittelstaet J, Baden C, Chan KC, Seitz C, Schlegel P, et al. Adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cells: an off-the-shelf cellular therapeutic for universal tumor targeting. Oncoimmunology. 2020;9(1):1825177.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Seitz CM, Mittelstaet J, Atar D, Hau J, Reiter S, Illi C, et al. Novel adapter CAR-T cell technology for precisely controllable multiplex cancer targeting. Oncoimmunology. 2021;10(1):2003532.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Werchau N, Kotter B, Criado-Moronati E, Gosselink A, Cordes N, Lock D, et al. Combined targeting of soluble latent TGF-ss and a solid tumor-associated antigen with adapter CAR T cells. Oncoimmunology. 2022;11(1):2140534.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS, Hardy IR, et al. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proc Natl Acad Sci USA. 2016;113(4):E459-68.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Viaud S, Ma JSY, Hardy IR, Hampton EN, Benish B, Sherwood L, et al. Switchable control over in vivo CAR T expansion, B cell depletion, and induction of memory. Proc Natl Acad Sci USA. 2018;115(46):E10898-906.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Raj D, Yang MH, Rodgers D, Hampton EN, Begum J, Mustafa A, et al. Switchable CAR-T cells mediate remission in metastatic pancreatic ductal adenocarcinoma. Gut. 2019;68(6):1052–64.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Landgraf KE, Williams SR, Steiger D, Gebhart D, Lok S, Martin DW, et al. convertibleCARs: a chimeric antigen receptor system for flexible control of activity and antigen targeting. Commun Biol. 2020;3(1):296.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Herzig E, Kim KC, Packard TA, Vardi N, Schwarzer R, Gramatica A, et al. Attacking latent HIV with convertibleCAR-T cells, a highly adaptable killing platform. Cell. 2019;179(4):880-894.e10.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Qi J, Tsuji K, Hymel D, Burke TR Jr, Hudecek M, Rader C, et al. Chemically programmable and switchable CAR-T therapy. Angew Chem Int Ed Engl. 2020;59(29):12178–85.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Minutolo NG, Sharma P, Poussin M, Shaw LC, Brown DP, Hollander EE, et al. Quantitative control of gene-engineered T-cell activity through the covalent attachment of targeting ligands to a universal immune receptor. J Am Chem Soc. 2020;142(14):6554–68.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu X, Wen J, Yi H, Hou X, Yin Y, Ye G, et al. Split chimeric antigen receptor-modified T cells targeting glypican-3 suppress hepatocellular carcinoma growth with reduced cytokine release. Ther Adv Med Oncol. 2020;12:1758835920910347.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lohmueller J, Butchy AA, Tivon Y, Kvorjak M, Miskov-Zivanov N, Deiters A, et al. Post-translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting. bioRxiv. 2020. https://doi.org/10.1101/2020.01.17.909895.

    Article 

    Google Scholar
     

  • Ruffo E, Kvorjak M, Adams E, Lohmueller J. Preclinical development of universal SNAP-CAR T cell therapy. J Immunol. 2021;206(Supplement):67.11.

    Article 

    Google Scholar
     

  • Bachmann M. The UniCAR system: a modular CAR T cell approach to improve the safety of CAR T cells. Immunol Lett. 2019;211:13–22.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Koristka S, Cartellieri M, Arndt C, Bippes CC, Feldmann A, Michalk I, et al. Retargeting of regulatory T cells to surface-inducible autoantigen La/SS-B. J Autoimmun. 2013;42:105–16.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nardi N, Brito-Zeron P, Ramos-Casals M, Aguilo S, Cervera R, Ingelmo M, et al. Circulating auto-antibodies against nuclear and non-nuclear antigens in primary Sjogren’s syndrome: prevalence and clinical significance in 335 patients. Clin Rheumatol. 2006;25(3):341–6.

    Article 
    PubMed 

    Google Scholar
     

  • Pan ZJ, Davis K, Maier S, Bachmann MP, Kim-Howard XR, Keech C, et al. Neo-epitopes are required for immunogenicity of the La/SS-B nuclear antigen in the context of late apoptotic cells. Clin Exp Immunol. 2006;143(2):237–48.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Malik S, Bruner GR, Williams-Weese C, Feo L, Scofield RH, Reichlin M, et al. Presence of anti-La autoantibody is associated with a lower risk of nephritis and seizures in lupus patients. Lupus. 2007;16(11):863–6.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Meyer JE, Loff S, Dietrich J, Spehr J, Jurado Jimenez G, von Bonin M, et al. Evaluation of switch-mediated costimulation in trans on universal CAR-T cells (UniCAR) targeting CD123-positive AML. Oncoimmunology. 2021;10(1):1945804.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Loff S, Dietrich J, Meyer JE, Riewaldt J, Spehr J, von Bonin M, et al. Rapidly switchable universal CAR-T cells for treatment of cd123-positive leukemia. Mol Ther Oncolytics. 2020;17:408–20.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wermke M, Kraus S, Ehninger A, Bargou RC, Goebeler ME, Middeke JM, et al. Proof of concept for a rapidly switchable universal CAR-T platform with UniCAR-T-CD123 in relapsed/refractory AML. Blood. 2021;137(22):3145–8.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bachmann D, Aliperta R, Bergmann R, Feldmann A, Koristka S, Arndt C, et al. Retargeting of UniCAR T cells with an in vivo synthesized target module directed against CD19 positive tumor cells. Oncotarget. 2018;9(7):7487–500.

    Article 
    PubMed 

    Google Scholar
     

  • Loureiro LR, Feldmann A, Bergmann R, Koristka S, Berndt N, Arndt C, et al. Development of a novel target module redirecting UniCAR T cells to Sialyl Tn-expressing tumor cells. Blood Cancer J. 2018;8(9):81.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Loureiro LR, Feldmann A, Bergmann R, Koristka S, Berndt N, Mathe D, et al. Extended half-life target module for sustainable UniCAR T-cell treatment of STn-expressing cancers. J Exp Clin Cancer Res. 2020;39(1):77.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Albert S, Arndt C, Feldmann A, Bergmann R, Bachmann D, Koristka S, et al. A novel nanobody-based target module for retargeting of T lymphocytes to EGFR-expressing cancer cells via the modular UniCAR platform. Oncoimmunology. 2017;6(4):e1287246.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jureczek J, Feldmann A, Bergmann R, Arndt C, Berndt N, Koristka S, et al. Highly efficient targeting of EGFR-Expressing tumor cells with UniCAR T cells via target modules based on cetuximab((R)). Onco Targets Ther. 2020;13:5515–27.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arndt C, Loureiro LR, Feldmann A, Jureczek J, Bergmann R, Mathe D, et al. UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells. Oncoimmunology. 2020;9(1):1743036.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pishali Bejestani E, Cartellieri M, Bergmann R, Ehninger A, Loff S, Kramer M, et al. Characterization of a switchable chimeric antigen receptor platform in a pre-clinical solid tumor model. Oncoimmunology. 2017;6(10):e1342909.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Feldmann A, Arndt C, Bergmann R, Loff S, Cartellieri M, Bachmann D, et al. Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology “UniCAR.” Oncotarget. 2017;8(19):31368–85.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mitwasi N, Feldmann A, Arndt C, Koristka S, Berndt N, Jureczek J, et al. “UniCAR”-modified off-the-shelf NK-92 cells for targeting of GD2-expressing tumour cells. Sci Rep. 2020;10(1):2141.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Feldmann A, Hoffmann A, Kittel-Boselli E, Bergmann R, Koristka S, Berndt N, et al. A novel revcar platform for switchable and gated tumor targeting. Blood. 2019;134(Supplement_1):5611. https://doi.org/10.1182/blood-2019-128436.

    Article 

    Google Scholar
     

  • Feldmann A, Hoffmann A, Bergmann R, Koristka S, Berndt N, Arndt C, et al. Versatile chimeric antigen receptor platform for controllable and combinatorial T cell therapy. Oncoimmunology. 2020;9(1):1785608.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kittel-Boselli E, Soto KEG, Loureiro LR, Hoffmann A, Bergmann R, Arndt C, et al. Targeting acute myeloid leukemia using the RevCAR platform: a programmable, switchable and combinatorial strategy. Cancers. 2021;13(19):4785.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mitwasi N, Hassan H, Arndt C, Loureiro L, Neuber C, Kegler A, et al. 45P The RevCAR T cell platform: a switchable and combinatorial therapeutic strategy for glioblastoma. Immuno-Oncol Technol. 2022. https://doi.org/10.1016/j.iotech.2022.100150.

    Article 

    Google Scholar
     

  • Cho JH, Collins JJ, Wong WW. Universal chimeric antigen receptors for multiplexed and logical control of T cell responses. Cell. 2018;173(6):1426-1438.e11.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cho JH, Okuma A, Sofjan K, Lee S, Collins JJ, Wong WW. Engineering advanced logic and distributed computing in human CAR immune cells. Nat Commun. 2021;12(1):792.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lajoie MJ, Boyken SE, Salter AI, Bruffey J, Rajan A, Langan RA, et al. Designed protein logic to target cells with precise combinations of surface antigens. Science. 2020;369(6511):1637–43.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Depil S, Duchateau P, Grupp SA, Mufti G, Poirot L. “Off-the-shelf” allogeneic CAR T cells: development and challenges. Nat Rev Drug Discov. 2020;19(3):185–99.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Caldwell KJ, Gottschalk S, Talleur AC. Allogeneic CAR cell therapy-more than a pipe dream. Front Immunol. 2020;11:618427.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dimitri A, Herbst F, Fraietta JA. Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing. Mol Cancer. 2022;21(1):78.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Park JJ, Lee KAV, Lam SZ, Tang K, Chen S. Genome engineering for next-generation cellular immunotherapies. Biochemistry. 2022. https://doi.org/10.1021/acs.biochem.2c00340.

    Article 
    PubMed 

    Google Scholar
     

  • Naeem M, Hazafa A, Bano N, Ali R, Farooq M, Razak SIA, et al. Explorations of CRISPR/Cas9 for improving the long-term efficacy of universal CAR-T cells in tumor immunotherapy. Life Sci. 2023;316:121409.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang H, Yu P, Tomar VS, Chen X, Atherton MJ, Lu Z, et al. Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors. Nat Cancer. 2022;3(7):808–20.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Uckun FM. Overcoming the immunosuppressive tumor microenvironment in multiple myeloma. Cancers. 2021;13(9):2018.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chung H, Jung H, Noh JY. Emerging approaches for solid tumor treatment using CAR-T cell therapy. Int J Mol Sci. 2021;22(22):12126.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang Z, McWilliams-Koeppen HP, Reza H, Ostberg JR, Chen W, Wang X, et al. 3D-organoid culture supports differentiation of human CAR(+) iPSCs into highly functional CAR T cells. Cell Stem Cell. 2022;29(4):515-527.e8.

    Article 
    PubMed 

    Google Scholar
     

  • Yang Y, Bi X, Gergis M, Yi D, Hsu J, Gergis U. Allogeneic chimeric antigen receptor T cells for hematologic malignancies. Hematol Oncol Stem Cell Ther. 2022;15(3):112–6.

    PubMed 

    Google Scholar
     

  • Demel I, Koristek Z, Motais B, Hajek R, Jelinek T. Natural killer cells: Innate immune system as a part of adaptive immunotherapy in hematological malignancies. Am J Hematol. 2022;97(6):802–17.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lee D, Rosenthal CJ, Penn NE, Dunn ZS, Zhou Y, Yang L. Human gammadelta T cell subsets and their clinical applications for cancer immunotherapy. Cancers. 2022;14(12):3005.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pan K, Farrukh H, Chittepu V, Xu H, Pan CX, Zhu Z. CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy. J Exp Clin Cancer Res. 2022;41(1):119.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rossi F, Fredericks N, Snowden A, Allegrezza MJ, Moreno-Nieves UY. Next generation natural killer cells for cancer immunotherapy. Front Immunol. 2022;13:886429.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Urbanska K, Lynn RC, Stashwick C, Thakur A, Lum LG, Powell DJ Jr. Targeted cancer immunotherapy via combination of designer bispecific antibody and novel gene-engineered T cells. J Transl Med. 2014;12:347.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Karches CH, Benmebarek MR, Schmidbauer ML, Kurzay M, Klaus R, Geiger M, et al. Bispecific antibodies enable synthetic agonistic receptor-transduced T cells for tumor immunotherapy. Clin Cancer Res. 2019;25(19):5890–900.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Thakur A, Scholler J, Kubicka E, Bliemeister ET, Schalk DL, June CH, et al. Bispecific antibody armed metabolically enhanced headless CAR T cells. Front Immunol. 2021;12:690437.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grada Z, Hegde M, Byrd T, Shaffer DR, Ghazi A, Brawley VS, et al. TanCAR: a novel bispecific chimeric antigen receptor for cancer immunotherapy. Mol Ther Nucleic Acids. 2013;2(7):e105.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li D, Hu Y, Jin Z, Zhai Y, Tan Y, Sun Y, et al. TanCAR T cells targeting CD19 and CD133 efficiently eliminate MLL leukemic cells. Leukemia. 2018;32(9):2012–6.

    Article 
    PubMed 

    Google Scholar
     

  • Khan AN, Chowdhury A, Karulkar A, Jaiswal AK, Banik A, Asija S, et al. Immunogenicity of CAR-T cell therapeutics: evidence, mechanism and mitigation. Front Immunol. 2022;13:886546.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • SD-Area Police Agencies to Bring Car-Repair Voucher Program to California

    SD-Area Police Agencies to Bring Car-Repair Voucher Program to California
    Lights On! program
    The San Diego-space regulation enforcement agencies partnered with the San Diego Padres
    Basis and Scripps Wellness to enable shell out for the initiative. Photo through @ChiefNisleit Twitter

    Officers with the San Diego Law enforcement Section and their counterparts in two neighboring metropolitan areas will before long commence providing motor vehicle homeowners enable in shelling out to swap burned-out headlights, tail lights, brake lights and convert alerts even though averting website traffic citations that can verify unaffordable for some reduce-profits motorists.

    As an alternative of issuing so-called “fix-it tickets” for failed vehicle lights, the SDPD and the Chula Vista and National Metropolis police departments are planning to offer you drivers vouchers that can be redeemed at collaborating automobile-support providers for up to $250 toward fixing the products, officers with the organizations introduced through a news conference Tuesday early morning.

    The company — aspect of a nationwide application named Lights On!, created by Minneapolis-based mostly nonprofit MicroGrants — will go into outcome domestically “in the coming weeks” as a way to enhance visitors basic safety and “mitigate what could grow to be a downward (fiscal) spiral for lower-earnings residents,” in accordance to a statement produced by the SDPD.

    The trio of San Diego-spot law enforcement businesses, the initially in the point out to indication on to the application, have partnered with the San Diego Padres Foundation and Scripps Wellness to assist spend for the initiative, with all the neighborhood donations to be matched by MicroGrants, according to organizers.

    The co-funding arrangement will make it possible for the law enforcement businesses to work the method for a few several years, give or just take, based on the cumulative charge of repairs and amount of redemption of the vouchers.

    “The San Diego Police Office is very pleased to be partnering with the Chula Vista and National Town law enforcement departments to be the first to carry the Lights On! method to California,” SDPD Chief David Nisleit claimed. “Lights On! is certainly an progressive option that will make our roads safer and guide decrease-cash flow local community members.”

    Town Information Provider contributed to this short article.