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

. 2023 Mar 15 ; 21 (1) : 197. [epub] 20230315

Jazyk angličtina Země Anglie, Velká Británie Médium electronic

Typ dokumentu časopisecké články, přehledy, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid36922828
Odkazy

PubMed 36922828
PubMed Central PMC10015723
DOI 10.1186/s12967-023-04041-6
PII: 10.1186/s12967-023-04041-6
Knihovny.cz E-zdroje

Cancer immunotherapies utilizing genetically engineered T cells have emerged as powerful personalized therapeutic agents showing dramatic preclinical and clinical results, particularly in hematological malignancies. Ectopically expressed chimeric antigen receptors (CARs) reprogram immune cells to target and eliminate cancer. However, CAR T cell therapy's success depends on the balance between effective anti-tumor activity and minimizing harmful side effects. To improve CAR T cell therapy outcomes and mitigate associated toxicities, scientists from different fields are cooperating in developing next-generation products using the latest molecular cell biology and synthetic biology tools and technologies. The immunotherapy field is rapidly evolving, with new approaches and strategies being reported at a fast pace. This comprehensive literature review aims to provide an up-to-date overview of the latest developments in controlling CAR T cell activity for improved safety, efficacy, and flexibility.

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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. doi: 10.1038/bcj.2016.61. PubMed DOI PMC

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. doi: 10.1158/2326-6066.CIR-14-0186. PubMed DOI PMC

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. doi: 10.3109/14653241003709686. PubMed DOI PMC

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. doi: 10.1038/mt.2010.24. PubMed DOI PMC

Ramos CA, Savoldo B, Dotti G. CD19-CAR trials. Cancer J. 2014;20(2):112–8. doi: 10.1097/PPO.0000000000000031. PubMed DOI PMC

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. doi: 10.1146/annurev-pharmtox-010814-124844. PubMed DOI

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. doi: 10.1016/j.ymthe.2017.03.002. PubMed DOI PMC

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. doi: 10.1182/blood-2017-06-793141. PubMed DOI PMC

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. doi: 10.1038/nrclinonc.2017.148. PubMed DOI PMC

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. doi: 10.1038/s41416-018-0325-1. PubMed DOI PMC

Sharma N, Reagan PM, Liesveld JL. Cytopenia after CAR-T cell therapy—a brief review of a complex problem. Cancers. 2022;14(6):1501. doi: 10.3390/cancers14061501. PubMed DOI PMC

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. doi: 10.1016/j.bulcan.2021.05.003. PubMed DOI

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. PubMed PMC

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. doi: 10.1186/s12943-019-1057-4. PubMed DOI PMC

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. doi: 10.3390/ijms21228620. PubMed DOI PMC

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. doi: 10.3389/fimmu.2022.1032403. PubMed DOI PMC

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. doi: 10.1063/5.0073746. PubMed DOI PMC

Madderson O, Teixeira AP, Fussenegger M. Emerging mammalian gene switches for controlling implantable cell therapies. Curr Opin Chem Biol. 2021;1(64):98–105. doi: 10.1016/j.cbpa.2021.05.012. PubMed DOI

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. doi: 10.1007/s00262-019-02399-5. PubMed DOI PMC

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. doi: 10.3390/cancers12051302. PubMed DOI PMC

Liu D, Zhao J, Song Y. Engineering switchable and programmable universal CARs for CAR T therapy. J Hematol Oncol. 2019;12(1):69. doi: 10.1186/s13045-019-0763-0. PubMed DOI PMC

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. doi: 10.3390/ijms21197222. PubMed DOI PMC

Gamboa L, Zamat AH, Kwong GA. Synthetic immunity by remote control. Theranostics. 2020;10(8):3652–67. doi: 10.7150/thno.41305. PubMed DOI PMC

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. doi: 10.1021/acs.jmedchem.0c02054. PubMed DOI

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. doi: 10.3389/fonc.2022.832765. PubMed DOI PMC

Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016;127(26):3321–30. doi: 10.1182/blood-2016-04-703751. PubMed DOI PMC

Sahillioglu AC, Schumacher TN. Safety switches for adoptive cell therapy. Curr Opin Immunol. 2022;74:190–8. doi: 10.1016/j.coi.2021.07.002. PubMed DOI

Caliendo F, Dukhinova M, Siciliano V. Engineered cell-based therapeutics: synthetic biology meets immunology. Front Bioeng Biotechnol. 2019;7:43. doi: 10.3389/fbioe.2019.00043. PubMed DOI PMC

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. doi: 10.1080/17843286.2018.1545373. PubMed DOI

Heard A, Chang J, Warrington JM, Singh N. Advances in CAR design. Best Pract Res Clin Haematol. 2021;34(3):101304. doi: 10.1016/j.beha.2021.101304. PubMed DOI

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. doi: 10.1111/febs.15523. PubMed DOI PMC

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. doi: 10.1007/s12094-020-02490-9. PubMed DOI

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. doi: 10.3389/fimmu.2022.849759. PubMed DOI PMC

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. doi: 10.1186/s40364-022-00371-7. PubMed DOI PMC

Kyte JA. Strategies for improving the efficacy of CAR T cells in solid cancers. Cancers. 2022;14(3):571. doi: 10.3390/cancers14030571. PubMed DOI PMC

Schaft N. The landscape of CAR-T cell clinical trials against solid tumors—a comprehensive overview. Cancers. 2020;12(9):2567. doi: 10.3390/cancers12092567. PubMed DOI PMC

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. doi: 10.1371/journal.pone.0144787. PubMed DOI PMC

Sadelain M, Riviere I, Riddell S. Therapeutic T cell engineering. Nature. 2017;545(7655):423–31. doi: 10.1038/nature22395. PubMed DOI PMC

Brenner MJ, Cho JH, Wong NML, Wong WW. Synthetic biology: immunotherapy by design. Annu Rev Biomed Eng. 2018;20:95–118. doi: 10.1146/annurev-bioeng-062117-121147. PubMed DOI

June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379(1):64–73. doi: 10.1056/NEJMra1706169. PubMed DOI PMC

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. doi: 10.1038/s41587-019-0329-2. PubMed DOI

Park CH. Making potent CAR T cells using genetic engineering and synergistic agents. Cancers. 2021;13(13):3236. doi: 10.3390/cancers13133236. PubMed DOI PMC

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. doi: 10.1186/s40580-022-00310-0. PubMed DOI PMC

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. doi: 10.3389/fphar.2014.00254. PubMed DOI PMC

Tey SK. Adoptive T-cell therapy: adverse events and safety switches. Clin Transl Immunol. 2014;3(6):e17. doi: 10.1038/cti.2014.11. PubMed DOI PMC

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. doi: 10.1097/CJI.0000000000000134. PubMed DOI

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. doi: 10.1182/blood-2004-11-4564. PubMed DOI PMC

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. doi: 10.1182/blood-2005-08-3503. PubMed DOI PMC

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. doi: 10.1016/S0092-8674(00)81477-4. PubMed DOI

Tiberghien P. Use of suicide genes in gene therapy. J Leukoc Biol. 1994;56(2):203–9. doi: 10.1002/jlb.56.2.203. PubMed DOI

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. doi: 10.1073/pnas.96.15.8699. PubMed DOI PMC

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. doi: 10.1016/S0960-9822(02)00607-3. PubMed DOI

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. doi: 10.1089/10430340050015798. PubMed DOI

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. doi: 10.1089/hum.2018.180. PubMed DOI PMC

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. doi: 10.1016/j.cellimm.2021.104342. PubMed DOI

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. PubMed

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. doi: 10.1089/hgtb.2012.147. PubMed DOI

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. doi: 10.1038/s41587-020-0580-6. PubMed DOI

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. doi: 10.1016/j.ymthe.2017.06.026. PubMed DOI PMC

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. PubMed PMC

Putyrski M, Schultz C. Protein translocation as a tool: the current rapamycin story. FEBS Lett. 2012;586(15):2097–105. doi: 10.1016/j.febslet.2012.04.061. PubMed DOI

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. doi: 10.1007/s00282-997-0273-3. PubMed DOI

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. doi: 10.1046/j.1365-2796.2001.00809.x. PubMed DOI

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. doi: 10.1016/S1470-2045(09)70074-9. PubMed DOI

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. doi: 10.1182/blood-2006-04-015230. PubMed DOI

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. doi: 10.1182/blood-2013-04-493361. PubMed DOI

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. doi: 10.1038/nm0296-216. PubMed DOI

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. doi: 10.1089/hum.2010.014. PubMed DOI

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. doi: 10.1007/s00109-011-0777-8. PubMed DOI

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. doi: 10.1016/S0092-8674(00)80434-1. PubMed DOI

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. doi: 10.1016/j.omto.2018.12.009. PubMed DOI PMC

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. doi: 10.3389/fonc.2019.00151. PubMed DOI PMC

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. doi: 10.3390/ijms21072481. PubMed DOI PMC

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. doi: 10.1182/blood-2007-02-072843. PubMed DOI PMC

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. doi: 10.4049/jimmunol.180.9.6365. PubMed DOI

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. doi: 10.1016/j.ymthe.2017.01.011. PubMed DOI PMC

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. doi: 10.1038/leu.2010.75. PubMed DOI PMC

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. doi: 10.1056/NEJMoa1106152. PubMed DOI PMC

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. doi: 10.1371/journal.pone.0082742. PubMed DOI PMC

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. doi: 10.1182/blood-2015-02-628354. PubMed DOI PMC

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. doi: 10.3389/fphar.2014.00235. PubMed DOI PMC

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. doi: 10.1089/10430349950016924. PubMed DOI

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. doi: 10.1182/blood.V97.5.1249.h8001249_1249_1257. PubMed DOI

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. doi: 10.1038/sj.gt.3301977. PubMed DOI

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. doi: 10.1182/blood-2003-08-2908. PubMed DOI

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. doi: 10.1182/blood-2014-01-545020. PubMed DOI

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. doi: 10.1038/s41598-018-27264-w. PubMed DOI PMC

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. doi: 10.1038/s41434-021-00220-6. PubMed DOI PMC

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. doi: 10.1073/pnas.91.17.8302. PubMed DOI PMC

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. PubMed

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. PubMed

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. PubMed

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. doi: 10.1158/2326-6066.CIR-16-0043. PubMed DOI

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. doi: 10.3390/ijms19113455. PubMed DOI PMC

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. doi: 10.1371/journal.pone.0197349. PubMed DOI PMC

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. doi: 10.1038/s41598-020-70022-0. PubMed DOI PMC

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. doi: 10.3390/nu10121892. PubMed DOI PMC

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. doi: 10.1073/pnas.2106612118. PubMed DOI PMC

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. doi: 10.3390/cancers13194741. PubMed DOI PMC

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. doi: 10.1038/ncomms5404. PubMed DOI PMC

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. doi: 10.1038/nchembio.2063. PubMed DOI PMC

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. doi: 10.1126/sciadv.aay9209. PubMed DOI PMC

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. doi: 10.1073/pnas.1714900115. PubMed DOI PMC

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 doi: 10.1038/s41551-021-00781-2. PubMed DOI PMC

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 doi: 10.1038/s41551-021-00779-w. PubMed DOI PMC

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. doi: 10.1038/srep39833. PubMed DOI PMC

Prinzing B, Krenciute G. Hypoxia-inducible CAR expression: an answer to the on-target/off-tumor dilemma? Cell Rep Med. 2021;2(4):100244. doi: 10.1016/j.xcrm.2021.100244. PubMed DOI PMC

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. doi: 10.1186/s40364-020-00238-9. PubMed DOI PMC

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. doi: 10.1016/j.xcrm.2021.100227. PubMed DOI PMC

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. doi: 10.1038/s42003-020-0848-x. PubMed DOI PMC

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. doi: 10.1016/j.cell.2016.01.012. PubMed DOI PMC

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. doi: 10.1016/j.cell.2016.01.011. PubMed DOI PMC

Chen LC, Hou AJ, Chen YY. Getting better mileage with logically primed CARs. Med. 2021;2(7):785–7. doi: 10.1016/j.medj.2021.06.002. PubMed DOI

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. doi: 10.1016/j.ccell.2019.02.003. PubMed DOI PMC

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. doi: 10.1038/s41467-020-20785-x. PubMed DOI PMC

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. PubMed PMC

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. doi: 10.1126/scitranslmed.abd8836. PubMed DOI PMC

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. doi: 10.1186/s12896-019-0537-3. PubMed DOI PMC

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. doi: 10.1021/acssynbio.1c00007. PubMed DOI

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. doi: 10.1016/j.chembiol.2020.11.012. PubMed DOI

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. doi: 10.1126/scitranslmed.abb6295. PubMed DOI PMC

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. doi: 10.1182/blood-2018-01-821769. PubMed DOI PMC

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. doi: 10.1021/acssynbio.9b00476. PubMed DOI

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. doi: 10.1126/science.aab4077. PubMed DOI PMC

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. doi: 10.1172/jci.insight.124430. PubMed DOI PMC

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. doi: 10.1073/pnas.1911154117. PubMed DOI PMC

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. doi: 10.1038/s41467-020-17970-3. PubMed DOI PMC

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. doi: 10.1038/srep18950. PubMed DOI PMC

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. doi: 10.1038/s41565-021-00982-5. PubMed DOI PMC

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. doi: 10.1158/2326-6066.CIR-21-0095. PubMed DOI PMC

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. doi: 10.1038/s41587-019-0403-9. PubMed DOI

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. doi: 10.1038/s41598-021-01418-9. PubMed DOI PMC

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. doi: 10.1038/s41467-020-20671-6. PubMed DOI PMC

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. doi: 10.1126/scitranslmed.3006597. PubMed DOI PMC

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. doi: 10.1016/j.molimm.2020.09.012. PubMed DOI

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. doi: 10.1073/pnas.2022410118. PubMed DOI PMC

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 doi: 10.3390/cancers12092612. PubMed DOI PMC

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 doi: 10.1016/j.ymthe.2021.11.013. PubMed DOI PMC

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. doi: 10.1158/2643-3230.BCD-20-0208. PubMed DOI PMC

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. doi: 10.1182/blood-2019-121973. PubMed DOI

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. doi: 10.1182/blood-2005-09-3775. PubMed DOI

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. doi: 10.1158/0008-5472.CAN-13-1365. PubMed DOI

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. doi: 10.1158/2326-6066.CIR-13-0099-T. PubMed DOI

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. doi: 10.1016/j.jcyt.2015.10.014. PubMed DOI

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. doi: 10.1158/1078-0432.CCR-12-1449. PubMed DOI

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. doi: 10.1021/jacs.5b00106. PubMed DOI

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. doi: 10.1002/anie.201601902. PubMed DOI PMC

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. doi: 10.1073/pnas.1524193113. PubMed DOI PMC

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. doi: 10.1016/j.chembiol.2020.10.004. PubMed DOI

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. PubMed PMC

Urbanska K, Powell DJ. Development of a novel universal immune receptor for antigen targeting: to Infinity and beyond. Oncoimmunology. 2012;1(5):777–9. doi: 10.4161/onci.19730. PubMed DOI PMC

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. doi: 10.1158/0008-5472.CAN-11-3890. PubMed DOI PMC

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. doi: 10.1080/2162402X.2017.1368604. PubMed DOI PMC

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. PubMed

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. doi: 10.1080/2162402X.2020.1825177. PubMed DOI PMC

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. doi: 10.1080/2162402X.2021.2003532. PubMed DOI PMC

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. doi: 10.1080/2162402X.2022.2140534. PubMed DOI PMC

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. doi: 10.1073/pnas.1524155113. PubMed DOI PMC

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. doi: 10.1073/pnas.1810060115. PubMed DOI PMC

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. doi: 10.1136/gutjnl-2018-316595. PubMed DOI PMC

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. doi: 10.1038/s42003-020-1021-2. PubMed DOI PMC

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. doi: 10.1016/j.cell.2019.10.002. PubMed DOI PMC

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. doi: 10.1002/anie.202005432. PubMed DOI PMC

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. doi: 10.1021/jacs.9b11622. PubMed DOI PMC

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. doi: 10.1177/1758835920910347. PubMed DOI PMC

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 doi: 10.1101/2020.01.17.909895. PubMed DOI PMC

Ruffo E, Kvorjak M, Adams E, Lohmueller J. Preclinical development of universal SNAP-CAR T cell therapy. J Immunol. 2021;206(Supplement):67.11. doi: 10.4049/jimmunol.206.Supp.67.11. PubMed DOI

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. doi: 10.1016/j.imlet.2019.05.003. PubMed DOI

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. doi: 10.1016/j.jaut.2013.01.002. PubMed DOI

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. doi: 10.1007/s10067-005-0059-3. PubMed DOI

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. doi: 10.1111/j.1365-2249.2005.03001.x. PubMed DOI PMC

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. doi: 10.1177/0961203307083365. PubMed DOI

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. doi: 10.1080/2162402X.2021.1945804. PubMed DOI PMC

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. doi: 10.1016/j.omto.2020.04.009. PubMed DOI PMC

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. doi: 10.1182/blood.2020009759. PubMed DOI PMC

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. doi: 10.18632/oncotarget.23556. PubMed DOI PMC

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. doi: 10.1038/s41408-018-0113-4. PubMed DOI PMC

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. doi: 10.1186/s13046-020-01572-4. PubMed DOI PMC

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. doi: 10.1080/2162402X.2017.1287246. PubMed DOI PMC

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. doi: 10.2147/OTT.S245169. PubMed DOI PMC

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. doi: 10.1080/2162402X.2020.1743036. PubMed DOI PMC

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. doi: 10.1080/2162402X.2017.1342909. PubMed DOI PMC

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. doi: 10.18632/oncotarget.15572. PubMed DOI PMC

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. doi: 10.1038/s41598-020-59082-4. PubMed DOI PMC

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. doi: 10.1182/blood-2019-128436. DOI

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. doi: 10.1080/2162402X.2020.1785608. PubMed DOI PMC

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. doi: 10.3390/cancers13194785. PubMed DOI PMC

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 doi: 10.1016/j.iotech.2022.100150. DOI

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. doi: 10.1016/j.cell.2018.03.038. PubMed DOI PMC

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. doi: 10.1038/s41467-021-21078-7. PubMed DOI PMC

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. doi: 10.1126/science.aba6527. PubMed DOI PMC

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. doi: 10.1038/s41573-019-0051-2. PubMed DOI

Caldwell KJ, Gottschalk S, Talleur AC. Allogeneic CAR cell therapy-more than a pipe dream. Front Immunol. 2020;11:618427. doi: 10.3389/fimmu.2020.618427. PubMed DOI PMC

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. doi: 10.1186/s12943-022-01559-z. PubMed DOI PMC

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

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. doi: 10.1016/j.lfs.2023.121409. PubMed DOI

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. doi: 10.1038/s43018-022-00383-0. PubMed DOI PMC

Uckun FM. Overcoming the immunosuppressive tumor microenvironment in multiple myeloma. Cancers. 2021;13(9):2018. doi: 10.3390/cancers13092018. PubMed DOI PMC

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. doi: 10.3390/ijms222212126. PubMed DOI PMC

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. doi: 10.1016/j.stem.2022.02.009. PubMed DOI PMC

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

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. doi: 10.1002/ajh.26529. PubMed DOI

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. doi: 10.3390/cancers14123005. PubMed DOI PMC

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. doi: 10.1186/s13046-022-02327-z. PubMed DOI PMC

Rossi F, Fredericks N, Snowden A, Allegrezza MJ, Moreno-Nieves UY. Next generation natural killer cells for cancer immunotherapy. Front Immunol. 2022;13:886429. doi: 10.3389/fimmu.2022.886429. PubMed DOI PMC

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. doi: 10.1186/s12967-014-0347-2. PubMed DOI PMC

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. doi: 10.1158/1078-0432.CCR-18-3927. PubMed DOI PMC

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. doi: 10.3389/fimmu.2021.690437. PubMed DOI PMC

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. doi: 10.1038/mtna.2013.32. PubMed DOI PMC

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. doi: 10.1038/s41375-018-0212-z. PubMed DOI

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. doi: 10.3389/fimmu.2022.886546. PubMed DOI PMC

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