Open Access

CAR-T Cells – Main Steps for Obtaining a Proper “Live Drug” Adoptive Therapy


Cite

Majzner RG, Mackall CL. Clinical lessons learned from the first leg of the CAR T cell journey. Nat Med. 2019;25(9):1341-55. https://doi.org/10.1038/s41591-019-0564-6 PMid:31501612 Search in Google Scholar

Cappell KM, Kochenderfer JN. A comparison of chimeric antigen receptors containing CD28 versus 4-1BB costimulatory domains. Nat Rev Clin Oncol. 2021;18(11):715-27. https://doi.org/10.1038/s41571-021-00530-z PMid:34230645 Search in Google Scholar

Brudno JN, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for lymphoma. Nat Rev Clin Oncol. 2018;15(1):31-46. https://doi.org/10.1038/nrclinonc.2017.128 PMid:28857075 Search in Google Scholar

Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989;86(24):10024-8. https://doi.org/10.1073/pnas.86.24.10024 PMid:2513569 Search in Google Scholar

Maher J, Brentjens RJ, Gunset G, Rivière I, Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta/CD28 receptor. Nat Biotechnol. 2002;20(1):70-5. https://doi.org/10.1038/nbt0102-70 PMid:11753365 Search in Google Scholar

Albinger N, Hartmann J, Ullrich E. Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany. Gene Ther. 2021;28(9):513-27. https://doi.org/10.1038/s41434-021-00246-w PMid:33753909 Search in Google Scholar

Deming D, Wang K, Wei C, Feng D, Liu Y, He Q, et al. The BCMA-targeted fourth-generation CAR-T cells secreting IL-7 and CCL19 for therapy of refractory/recurrent multiple myeloma. Front Immunol. 2021;12:609421. https://doi.org/10.3389/fimmu.2021.609421 PMid:33767695 Search in Google Scholar

Tian Y, Li Y, Shao Y, Zhang Y. Gene modification strategies for next-generation CAR T cells against solid cancers. J Hematol Oncol. 2020;13(1):54. https://doi.org/10.1186/s13045-020-00890-6 PMid:32423475 Search in Google Scholar

Mikkilineni L, Kochenderfer JN. CAR T cell therapies for patients with multiple myeloma. Nat Rev Clin Oncol. 2021;18(2):71-84. https://doi.org/10.1038/s41571-020-0427-6 PMid:32978608 Search in Google Scholar

Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with b-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439-48. https://doi.org/10.1056/NEJMoa1709866 PMid:29385370 Search in Google Scholar

Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): A single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31-42. https://doi.org/10.1016/S1470-2045(18)30864-7 PMid:30518502 Search in Google Scholar

Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396(10254):839-52. https://doi.org/10.1016/S0140-6736(20)31366-0 PMid:32888407 Search in Google Scholar

Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382(14):1331-42. https://doi.org/10.1056/NEJMoa1914347 PMid:32242358 Search in Google Scholar

Feigal EG, Cosenza ME. Cellular-based therapies. In: Translational Medicine. United States: CRC Press; 2021. p. 359-80. Search in Google Scholar

Munshi NC, Anderson LD Jr., Shah N, Madduri D, Berdeja J, Lonial S, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-16. https://doi.org/10.1056/NEJMoa2024850 PMid:33626253 Search in Google Scholar

Martin T, Usmani SZ, Berdeja JG, Agha M, Cohen AD, Hari P, et al. Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-Cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-Year follow-up. J Clin Oncol. 2023;41(6):1265-74. https://doi.org/10.1200/JCO.22.00842 PMid:35658469 Search in Google Scholar

Fowler NH, Dickinson M, Dreyling M, Martinez-Lopez J, Kolstad A, Butler J, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: The phase 2 ELARA trial. Nat Med. 2022;28(2):325-32. https://doi.org/10.1038/s41591-021-01622-0 PMid:34921238 Search in Google Scholar

Cappell KM, Kochenderfer JN. Long-term outcomes following CAR T cell therapy: What we know so far. Nat Rev Clin Oncol. 2023;20:359-71. https://doi.org/10.1038/s41571-023-00754-1 PMid:37055515 Search in Google Scholar

Jacobson CA, Chavez JC, Sehgal AR, William BM, Munoz J, Salles G, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): A single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91-103. https://doi.org/10.1016/S1470-2045(21)00591-X PMid:34895487 Search in Google Scholar

Crump M, Neelapu SS, Farooq U, Van Den Neste E, Kuruvilla J, Westin J, et al. Outcomes in refractory difuse large B-cell lymphoma: Results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-8. https://doi.org/10.1182/blood-2017-03-769620 PMid:28774879 Search in Google Scholar

Shah BD, Ghobadi A, Oluwole OO, Logan AC, Boissel N, Cassaday RD, et al. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: Phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. Lancet. 2021;398(10299):491-502. https://doi.org/10.1016/S0140-6736(21)01222-8 PMid:34097852 Search in Google Scholar

Brudno JN, Kochenderfer JN. Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management. Blood Rev. 2019;34:45-55. https://doi.org/10.1016/j.blre.2018.11.002 PMid:30528964 Search in Google Scholar

Amini L, Silbert SK, Maude SL, Nastoupil LJ, Ramos CA, Brentjens RJ, et al. Preparing for CAR T cell therapy: Patient selection, bridging therapies and lymphodepletion. Nat Rev Clin Oncol. 2022;19(5):342-55. https://doi.org/10.1038/s41571-022-00607-3 PMid:35318469 Search in Google Scholar

Yip A, Webster RM. The market for chimeric antigen receptor T cell therapies. Nat Rev Drug Discov. 2018;17(3):161-2. https://doi.org/10.1038/nrd.2017.266 PMid:29375140 Search in Google Scholar

Albelda SM. CAR T cell therapy for patients with solid tumours: Key lessons to learn and unlearn. Nat Rev Clin Oncol. 2024;21:47-66. https://doi.org/10.1038/s41571-023-00832-4 PMid:37904019 Search in Google Scholar

Abou-el-Enein M, Elsallab M, Feldman SA, Andrew D. Fesnak AD, Heslop HE, et al. Scalable manufacturing of CAR T cells for cancer immunotherapy. Blood Cancer Discov. 2021;2(5):408-22. https://doi.org/10.1158/2643-3230.BCD-21-0084 PMid:34568831 Search in Google Scholar

Lin JK, Muffly LS, Spinner MA, Barnes JI, Owens DK, Goldhaber-Fiebert JD. Cost effectiveness of chimeric antigen receptor T-cell therapy in multiply relapsed or refractory adult large B-cell lymphoma. J Clin Oncol. 2019;37(24):2105-19. https://doi.org/10.1200/JCO.18.02079 PMid:31157579 Search in Google Scholar

Engstad CS, Gutteberg TJ, Osterud B. Modulation of blood cell activation by four commonly used anticoagulants. Thromb Haemost. 1997;77(4):690-6. PMid:9134644 Search in Google Scholar

McFarland DC, Zhang C, Thomas HC, Ratliff TL. Confounding effects of platelets on flow cytometric analysis and cellsorting experiments using blood-derived cells. Cytometry A. 2006;69:86-94. https://doi.org/10.1002/cyto.a.20207 PMid:16419063 Search in Google Scholar

Fesnak A, Lin C, Siegel DL, Maus MV. CAR-T cell therapies from the transfusion medicine perspective. Transfus Med Rev. 2016;30(3):139-45. https://doi.org/10.1016/j.tmrv.2016.03.001 PMid:27067907 Search in Google Scholar

Atanackovic D, Radhakrishnan SV, Bhardwaj N, Luetkens T. Chimeric antigen receptor (CAR) therapy for multiple myeloma. Br J Haematol. 2016;172(5):685-98. https://doi.org/10.1111/bjh.13889 PMid:26791002 Search in Google Scholar

Wang Z, Chen C, Wang L, Jia Y, Qin Y. Chimeric antigen receptor T-cell therapy for multiple myeloma. Front Immunol. 2022;13:1050522. https://doi.org/10.3389/fimmu.2022.1050522 PMid:36618390 Search in Google Scholar

Wang QS, Wang Y, Lv HY, Han QW, Fan H, Guo B, et al. Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther. 2015;23(1):184-91. https://doi.org/10.1038/mt.2014.164 PMid:25174587 Search in Google Scholar

Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ, et al. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood. 2016;128(13):1688-700. https://doi.org/10.1182/blood-2016-04-711903 PMid:27412889 Search in Google Scholar

Hollyman D, Stefanski J, Przybylowski M, Bartido S, Borquez-Ojeda O, Taylor C, et al. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy. J Immunother. 2009;32(2):169-80. https://doi.org/10.1097/CJI.0b013e318194a6e8 PMid:19238016 Search in Google Scholar

Turtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M, et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest. 2016;126(6):2123-38. https://doi.org/10.1172/JCI85309 PMid:27111235 Search in Google Scholar

El Marabti E, Abdel-Wahab O. Enhancing CD19 chimeric antigen receptor T cells through memory-enriched T cells. Clin Cancer Res. 2023;29(4):694-6. https://doi.org/10.1158/1078-0432.CCR-22-3232 PMid:36507801 Search in Google Scholar

Arcangeli S, Bove C, Mezzanotte C, Camisa B, Falcone L, Manfredi F, et al. CAR T cell manufacturing from naive/stem memory T lymphocytes enhances antitumor responses while curtailing cytokine release syndrome. J Clin Invest. 2022;132(12):e150807. https://doi.org/10.1172/JCI150807 PMid:35503659 Search in Google Scholar

Singh H, Figliola MJ, Dawson MJ, Olivares S, Zhang L, Yang G, et al. Manufacture of clinical-grade CD19-specific T cells stably expressing chimeric antigen receptor using sleeping beauty system and artificial antigen presenting cells. PLoS One. 2013;8(5):e64138. https://doi.org/10.1371/journal.pone.0064138 PMid:23741305 Search in Google Scholar

Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13(4):227-42. https://doi.org/10.1038/nri3405 PMid:23470321 Search in Google Scholar

Levine BL. Performance-enhancing drugs: Design and production of redirected chimeric antigen receptor (CAR) T cells. Cancer Gene Ther. 2015;22(2):79-84. https://doi.org/10.1038/cgt.2015.5 PMid:25675873 Search in Google Scholar

Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12(6):492-499. https://doi.org/10.1038/ni.2035 PMid:21739672 Search in Google Scholar

Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, et al. A human memory T cell subset with stem cell-like properties. Nat Med. 2011;17(10):1290-7. https://doi.org/10.1038/nm.2446 PMid:21926977 Search in Google Scholar

Barrett DM, Singh N, Liu X, Jiang S, June CH, Grupp SA, et al. Relation of clinical culture method to T-cell memory status and efficacy in xenograft models of adoptive immunotherapy. Cytotherapy. 2014;16(5):619-30. https://doi.org/10.1016/j.jcyt.2013.10.013 PMid:24439255 Search in Google Scholar

Ghassemi S, Bedoya F, Nunez-Cruz S, June C, Melenhorst J, Milone M. Shortened T cell culture with IL-7 and IL-15 provides the most potent chimeric antigen receptor (CAR)-modified T cells for adoptive immunotherapy. Cancer Immunother Cancer Vaccines. 2016;24(Suppl 1):S79. https://doi.org/10.1016/S1525-0016(16)33012-X Search in Google Scholar

Ukrainskaya VM, Rubtsov YP, Pershin DS, Podoplelova NA, Terekhov SS, Yaroshevich I, et al. Antigen-specific stimulation and expansion of CAR-T cells using membrane vesicles as target cell surrogates. Small. 2021;17(45):2102643. https://doi.org/10.1002/smll.202102643 PMid:34605165 Search in Google Scholar

Ghassemi S, Durgin JS, Nunez-Cruz S, Patel J, Leferovich J, Pinzone M, et al. Rapid manufacturing of non-activated potent CAR T cells. Nat Biomed Eng. 2022;6(2):118-28. https://doi.org/10.1038/s41551-021-00842-6 PMid:35190680 Search in Google Scholar

Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3(95):95ra73. https://doi.org/10.1126/scitranslmed.3002842 PMid:21832238 Search in Google Scholar

Casati A, Varghaei-Nahvi A, Feldman SA, Assenmacher M, Rosenberg SA, Dudley ME, et al. Clinical-scale selection and viral transduction of human naïve and central memory CD8+ T cells for adoptive cell therapy of cancer patients. Cancer Immunol Immunother. 2013;62(10):1563-73. https://doi.org/10.1007/s00262-013-1459-x PMid:23903715 Search in Google Scholar

Deeks SG, Wagner B, Anton PA, Mitsuyasu RT, Scadden DT, Huang C, et al. A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy. Mol Ther. 2002;5(6):788-97. https://doi.org/10.1006/mthe.2002.0611 PMid:12027564 Search in Google Scholar

Kebriaei P, Huls H, Singh H, Olivares S, Figliola M, Maiti S, et al. Adoptive therapy using sleeping beauty gene transfer system and artificial antigen presenting cells to manufacture T cells expressing CD19-specific chimeric antigen receptor. Blood. 2014;124:311. https://doi.org/10.1371/journal.pone.0064138 Search in Google Scholar

Cruz CR, Micklethwaite KP, Savoldo B, Ramos CA, Lam S, Ku S, et al. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: A phase 1 study. Blood. 2013;122(17):2965-73. https://doi.org/10.1182/blood-2013-06-506741 PMid:24030379 Search in Google Scholar

Lana MG, Strauss BE. Production of lentivirus for the establishment of CAR-T cells. Methods Mol Biol. 2020;2086:61-7. https://doi.org/10.1007/978-1-0716-0146-4_4 PMid:31707667 Search in Google Scholar

Brentjens RJ, Riviere I, Park JH, Davila ML, Wang X, Stefanski J, et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011;118(18):4817-28. https://doi.org/10.1182/blood-2011-04-348540 PMid:21849486 Search in Google Scholar

Ghorashian S, Pule M, Amrolia P. CD19 chimeric antigen receptor T cell therapy for haematological malignancies. Br J Haematol. 2015;169(4):463-78. https://doi.org/10.1111/bjh.13340 PMid:25753571 Search in Google Scholar

Hamada M, Nishio N, Okuno Y, Suzuki S, Kawashima N, Muramatsu H, et al. Integration mapping of piggyBac-Mediated CD19 chimeric antigen receptor T cells analyzed by novel tagmentation-assisted PCR. EBioMedicine. 2018;34:18-26. https://doi.org/10.1016/j.ebiom.2018.07.008 PMid:30082227 Search in Google Scholar

Ramanayake S, Bilmon I, Bishop D, Dubosq MC, Blyth E, Clancy L, et al. Low-cost generation of Good Manufacturing Practice-grade CD19-specific chimeric antigen receptor-expressing T cells using piggyBac gene transfer and patient-derived materials. Cytotherapy. 2015;17(9):1251-67. https://doi.org/10.1016/j.jcyt.2015.05.013 PMid:26212611 Search in Google Scholar

Merten OW, Hebben M, Bovolenta C. Production of lentiviral vectors. Mol Ther Methods Clin Dev. 2016;3:16017. https://doi.org/10.1038/mtm.2016.17 PMid:27110581 Search in Google Scholar

Sanber KS, Knight SB, Stephen SL, Bailey R, Escors D, Minshull J, et al. Construction of stable packaging cell lines for clinical lentiviral vector production. Sci Rep. 2015;5:9021. https://doi.org/10.1038/srep09021 PMid:25762005 Search in Google Scholar

Wang X, Rivière I. Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies. Cancer Gene Ther. 2015;22(2):85-94. https://doi.org/10.1038/cgt.2014.81 PMid:25721207 Search in Google Scholar

Ivics Z, Hackett PB, Plasterk RH, Izsvák Z. Molecular reconstruction of sleeping beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell. 1997;91(4):501-10. https://doi.org/10.1016/s0092-8674(00)80436-5 PMid:9390559 Search in Google Scholar

Moretti A, Ponzo M, Nicolette CA, Tcherepanova IY, Biondi A, Magnani CF. The past, present, and future of non-viral CAR T cells. Front Immunol. 2022;13:867013. https://doi.org/10.3389/fimmu.2022.867013 PMid:35757746 Search in Google Scholar

Singh H, Figliola MJ, Dawson MJ, Huls H, Olivares S, Switzer K, et al. Reprogramming CD19-specific T cells with IL-21 signaling can improve adoptive immunotherapy of B-lineage malignancies. Cancer Res. 2011;71(10):3516-27. https://doi.org/10.1158/0008-5472.CAN-10-3843 PMid:21558388 Search in Google Scholar

Kebriaei P, Ciurea SO, Huls MH, Singh H, Olivares S, Su S, et al. Pre-emptive donor lymphocyte infusion with CD19-directed, CAR-modified T cells infused after allogeneic hematopoietic cell transplantation for patients with advanced CD19+ malignancies. Blood. 2015;126:862. Search in Google Scholar

Narayanavari SA, Chilkunda SS, Ivics Z, Izsvák Z. Sleeping Beauty transposition: From biology to applications. Crit Rev Biochem Mol Biol. 2017;52(1):18-44. https://doi.org/10.1080/10409238.2016.1237935 PMid:27696897 Search in Google Scholar

Zhang C, Liu J, Zhong JF, Zhang X. Engineering CAR-T cells. Biomark Res. 2017;5:22. https://doi.org/10.1186/s40364-017-0102-y PMid:28652918 Search in Google Scholar

Gogol-Doring A, Ammar I, Gupta S, Bunse M, Miskey C, Chen W, et al. Genome-wide profiling reveals remarkable parallels between insertion site selection properties of the MLV retrovirus and the piggyBac transposon in primary human CD4(+) T cells. Mol Ther. 2016;24(3):592-606. https://doi.org/10.1038/mt.2016.11 PMid:26755332 Search in Google Scholar

Park JR, Digiusto DL, Slovak M, Wright C, Naranjo A, Wagner J, et al. Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol Ther. 2007;15(4):825-33. https://doi.org/10.1038/sj.mt.6300104 PMid:17299405 Search in Google Scholar

Jensen MC, Popplewell L, Cooper LJ, DiGiusto D, Kalos M, Ostberg JR, et al. Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. Biol Blood Marrow Transpl. 2010;16(9):1245-56. https://doi.org/10.1016/j.bbmt.2010.03.014 PMid:20304086 Search in Google Scholar

Kaiser AD, Assenmacher M, Schroder B, Meyer M, Orentas R, Bethke U, et al. Towards a commercial process for the manufacture of genetically modified T cells for therapy. Cancer Gene Ther. 2015;22(2):72-8. https://doi.org/10.1038/cgt.2014.78 PMid:25613483 Search in Google Scholar

Tumaini B, Lee DW, Lin T, Castiello L, Stroncek DF, Mackall C, et al. Simplified process for the production of anti-CD19-CAR-engineered T cells. Cytotherapy. 2013;15(11):1406-15. https://doi.org/10.1016/j.jcyt.2013.06.003 PMid:23992830 Search in Google Scholar

Hanley PJ. Fresh versus frozen: Effects of cryopreservation on CAR T cells. Mol Ther. 2019;27(7):1213-4. https://doi.org/10.1016/j.ymthe.2019.06.001 PMid:31202635 Search in Google Scholar

Panch SR, Srivastava SK, Elavia N, McManus A, Liu S, Jin P, et al. Effect of cryopreservation on autologous chimeric antigen receptor T cell characteristics. Mol Ther. 2019;27(7):1275-85. https://doi.org/10.1016/j.ymthe.2019.05.015 PMid:31178392 Search in Google Scholar

Vormittag P, Gunn R, Ghorashian S, Veraitch FS. A guide to manufacturing CAR T cell therapies. Curr Opin Biotechnol. 2018;53:164-81. https://doi.org/10.1016/j.copbio.2018.01.025 PMid:29462761 Search in Google Scholar

eISSN:
1857-9388
Language:
English
Publication timeframe:
Volume Open
Journal Subjects:
Medicine, Basic Medical Science, Immunology, Clinical Medicine, Laboratory Medicine