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