1,822
Views
1
CrossRef citations to date
0
Altmetric
Immunotherapy - Cancer

Building safety into CAR-T therapy

ORCID Icon, & ORCID Icon
Article: 2275457 | Received 19 Jul 2023, Accepted 22 Oct 2023, Published online: 15 Nov 2023

References

  • Kershaw MH, Westwood JA, Parker LL, Wang G, Eshhar Z, Mavroukakis SA, White DE, Wunderlich JR, Canevari S, Rogers-Freezer L, et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res. 2006;12(20):6106–8. doi:10.1158/1078-0432.CCR-06-1183.
  • Lamers CHJ, Sleijfer S, Vulto AG, Kruit WHJ, Kliffen M, Debets R, Gratama JW, Stoter G, Oosterwijk E. Treatment of metastatic renal cell carcinoma with autologous T-Lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol. 2006;24(13):e20–e2. doi:10.1200/JCO.2006.05.9964.
  • Pinthus JH, Waks T, Kaufman-Francis K, Schindler DG, Harmelin A, Kanety H, Ramon J, Eshhar Z. Immuno-gene therapy of established prostate tumors using chimeric receptor-redirected human lymphocytes1. Cancer Res. 2003;63:2470–6.
  • Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia. N Engl J Med. 2011;365(8):725–33. doi:10.1056/NEJMoa1103849.
  • Sheth VS, Gauthier J. Taming the beast: CRS and ICANS after CAR T-cell therapy for ALL. Bone Marrow Transplant. 2021;56(3):552–66. doi:10.1038/s41409-020-01134-4.
  • Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625–38. doi:10.1016/j.bbmt.2018.12.758.
  • Rejeski K, Perez A, Sesques P, Hoster E, Berger C, Jentzsch L, Mougiakakos D, Frölich L, Ackermann J, Bücklein V, et al. CAR-HEMATOTOX: a model for CAR T-cell–related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138(24):2499–513. doi:10.1182/blood.2020010543.
  • Sterner RM, Sakemura R, Cox MJ, Yang N, Khadka RH, Forsman CL, Hansen MJ, Jin F, Ayasoufi K, Hefazi M, et al. GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts. Blood. 2019;133(7):697–709. doi:10.1182/blood-2018-10-881722.
  • Santomasso BD, Nastoupil LJ, Adkins S, Lacchetti C, Schneider BJ, Anadkat M, Atkins MB, Brassil KJ, Caterino JM, Chau I, et al. Management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy: ASCO guideline. J Clin Oncol. 2021;39(35):3978–92. doi:10.1200/JCO.21.01992.
  • Herrmann J. Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia. Nat Rev Cardiol. 2020;17(8):474–502. doi:10.1038/s41569-020-0348-1.
  • Wang Y, Qi K, Cheng H, Cao J, Shi M, Qiao J, Yan Z, Jing G, Pan B, Sang W, et al. Coagulation disorders after chimeric antigen receptor T cell therapy: analysis of 100 patients with relapsed and refractory hematologic malignancies. Biol Blood Marrow Transplant. 2020;26(5):865–75. doi:10.1016/j.bbmt.2019.11.027.
  • Hines MR, Knight TE, McNerney KO, Leick MB, Jain T, Ahmed S, Frigault MJ, Hill JA, Jain MD, Johnson WT, et al. Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Transplant Cell Ther. 2023;29(7):.e438.1–.e6. doi:10.1016/j.jtct.2023.03.006.
  • Hernandez I, Prasad V, Gellad WF. Total costs of chimeric antigen receptor T-cell immunotherapy. JAMA Oncol. 2018;4(7):994–6. doi:10.1001/jamaoncol.2018.0977.
  • Brudno JN, Lam N, Vanasse D, Shen Y-W, Rose JJ, Rossi J, Xue A, Bot A, Scholler N, Mikkilineni L, et al. Safety and feasibility of anti-CD19 CAR T cells with fully humanbinding domains in patients with B-cell lymphoma. Nat Med. 2020;26(2):270–80. doi:10.1038/s41591-019-0737-3.
  • Santomasso BD, Park JH, Salloum D, Riviere I, Flynn J, Mead E, Halton E, Wang X, Senechal B, Purdon T, et al. Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discov. 2018;8(8):958–71. doi:10.1158/2159-8290.CD-17-1319.
  • Gust J, Hay KA, Hanafi L-A, Li D, Myerson D, Gonzalez-Cuyar LF, Yeung C, Liles WC, Wurfel M, Lopez JA, et al. Endothelial activation and blood–brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discov. 2017;7(12):1404–19. doi:10.1158/2159-8290.CD-17-0698.
  • Parker KR, Migliorini D, Perkey E, Yost KE, Bhaduri A, Bagga P, Haris M, Wilson NE, Liu F, Gabunia K, et al. Single-cell analyses identify brain mural cells expressing CD19 as potential off-tumor targets for CAR-T immunotherapies. Cell. 2020;183(1):126–42.e17. doi:10.1016/j.cell.2020.08.022.
  • Cohen AD, Parekh S, Santomasso BD, Gállego Pérez-Larraya J, van de Donk NWCJ, Arnulf B, Mateos M-V, Lendvai N, Jackson CC, De Braganca KC, et al. Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies. Blood Cancer J. 2022;12(2). doi:10.1038/s41408-022-00629-1.
  • Mueller KT, Waldron E, Grupp SA, Levine JE, Laetsch TW, Pulsipher MA, Boyer MW, August KJ, Hamilton J, Awasthi R, et al. Clinical pharmacology of tisagenlecleucel in B-cell acute lymphoblastic leukemia. Clin Cancer Res. 2018;24(24):6175–84. doi:10.1158/1078-0432.CCR-18-0758.
  • Adkins R, Msn. Anp-C, Sherry: CAR T-cell therapy: adverse events and management. J Adv Pract Oncol. 2019;10(4):2019. doi:10.6004/jadpro.2019.10.4.11.
  • Mestermann K, Giavridis T, Weber J, Rydzek J, Frenz S, Nerreter T, Mades A, Sadelain M, Einsele H, Hudecek M, et al. The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells. Sci Transl Med. 2019;11(499):eaau5907. doi:10.1126/scitranslmed.aau5907.
  • Ruella M, Kenderian SS, Shestova O, Klichinsky M, Melenhorst JJ, Wasik MA, Lacey SF, June CH, Gill S. Kinase inhibitor ibrutinib to prevent cytokine-release syndrome after anti-CD19 chimeric antigen receptor T cells for B-cell neoplasms. Leukemia. 2017;31(1):246–8. doi:10.1038/leu.2016.262.
  • Pan J, Deng B, Ling Z, Song W, Xu J, Duan J, Wang Z, Chang AH, Feng X, Tan Y, et al. Ruxolitinib mitigates steroid-refractory CRS during CAR T therapy. J Cell Mol Med. 2021;25(2):1089–99. doi:10.1111/jcmm.16176.
  • Zi FM, Ye LL, Zheng JF, Cheng J, Wang QM. Using JAK inhibitor to treat cytokine release syndrome developed after chimeric antigen receptor T cell therapy for patients with refractory acute lymphoblastic leukemia: a case report. Medicine. 2021;100(19):e25786. doi:10.1097/MD.0000000000025786.
  • Turtle CJ, Hanafi L-A, Berger C, Gooley TA, Cherian S, Hudecek M, Sommermeyer D, Melville K, Pender B, Budiarto TM, 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. doi:10.1172/JCI85309.
  • Frigault M, Rotte A, Ansari A, Gliner B, Heery C, Shah B. Dose fractionation of CAR-T cells. A systematic review of clinical outcomes. J Exp Clin Canc Res. 2023;42(1):2023. doi:10.1186/s13046-022-02540-w.
  • Oluwole OO, Bouabdallah K, Muñoz J, De Guibert S, Vose JM, Bartlett NL, Lin Y, Deol A, McSweeney PA, Goy AH, et al. Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B‐cell lymphoma. Br J Haematol. 2021;194(4):690–700. doi:10.1111/bjh.17527.
  • Strati P, Li X, Deng Q, Feng L, Sun R, Jallouk A, Adkins S, Cain T, Johncy S, Steiner RE, et al. Primary analysis of a pilot study of prophylactic anakinra to mitigate CAR T cell-associated toxicity in patients with relapsed or refractory large B-cell lymphoma. Blood. 2022;140(Supplement 1):7493–5. doi:10.1182/blood-2022-157448.
  • Locke FL, Neelapu SS, Bartlett NL, Lekakis LJ, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, et al. Preliminary results of prophylactic tocilizumab after axicabtageneciloleucel (axi-cel; KTE-C19) treatment for patients with refractory, aggressive non-Hodgkin lymphoma (NHL). Blood. 2017;130(Suppl_1):1547–1547. doi:10.1182/blood.V130.Suppl_1.1547.1547.
  • Lamers CH, Sleijfer S, Van Steenbergen S, van Elzakker P, van Krimpen B, Groot C, Vulto A, den Bakker M, Oosterwijk E, Debets R, et al. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol Ther. 2013;21(4):904–12. doi:10.1038/mt.2013.17.
  • Linette GP, Stadtmauer EA, Maus MV, Rapoport AP, Levine BL, Emery L, Litzky L, Bagg A, Carreno BM, Cimino PJ, et al. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood. 2013;122(6):863–71. doi:10.1182/blood-2013-03-490565.
  • Abken H. Building on synthetic immunology and T cell engineering: a brief journey through the history of chimeric antigen receptors. Hum Gene Ther. 2021;32(19–20):1011–28. doi:10.1089/hum.2021.165.
  • 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(1). doi:10.1063/5.0073746.
  • Asmamaw Dejenie T, Markeshaw TG, Dessie Terefe G, Tadele Admasu, F., Wale Tesega, W., Chekol Abebe, E. Current updates on generations, approvals, and clinical trials of CAR T-cell therapy. Human Vaccin Immunother. 2022;18(6). doi:10.1080/21645515.2022.2114254.
  • Ghorashian S, Kramer AM, Onuoha S, Wright G, Bartram J, Richardson R, Albon SJ, Casanovas-Company J, Castro F, Popova B, et al. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med. 2019;25(9):1408–14. doi:10.1038/s41591-019-0549-5.
  • Myers RM, Li Y, Barz Leahy A, Barrett DM, Teachey DT, Callahan C, Fasano CC, Rheingold SR, DiNofia A, Wray L, et al. Humanized CD19-targeted chimeric antigen receptor (CAR) T cells in CAR-naive and CAR-exposed children and young adults with relapsed or refractory acute lymphoblastic leukemia. J Clin Oncol. 2021;39(27):3044–55. doi:10.1200/jco.20.03458. Epub 20210622. PubMed PMID: 34156874; PubMed Central PMCID: PMCPMC9851702.
  • Tan AHJ, Vinanica N, Campana D. Chimeric antigen receptor–T cells with cytokine neutralizing capacity. Blood Adv. 2020;4(7):1419–31. doi:10.1182/bloodadvances.2019001287.
  • Brudno JN, Lam N, Vanasse D, Y-W S, Rose JJ, Rossi J, Xue A, Bot A, Scholler N, Mikkilineni L, et al. Safety and feasibility of anti-CD19 CAR T cells with fully humanbinding domains in patients with B-cell lymphoma. Nat Med. 2020;26(2):270–80. doi:10.1038/s41591-019-0737-3.
  • Lanitis E, Poussin M, Klattenhoff AW, Song D, Sandaltzopoulos R, June CH, Powell DJ Jr. Chimeric antigen receptor T cells with dissociated signaling domains exhibit focused antitumor activity with reduced potential for toxicity in vivo. Cancer Immunol Res. 2013;1(1):43–53. doi:10.1158/2326-6066.Cir-13-0008.
  • Kittel-Boselli E, Soto KEG, Loureiro LR, Hoffmann A, Bergmann R, Arndt C, Koristka S, Mitwasi N, Kegler A, Bartsch T, 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.
  • Salzer B, Schueller CM, Zajc CU, Peters T, Schoeber MA, Kovacic B, Buri MC, Lobner E, Dushek O, Huppa JB, 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.
  • 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):ra215172–ra215172. doi:10.1126/scitranslmed.3006597.
  • Hwang MS, Mog BJ, Douglass J, Pearlman AH, Hsiue E-C, Paul S, DiNapoli SR, Konig MF, Pardoll DM, Gabelli SB, et al. Targeting loss of heterozygosity for cancer-specific immunotherapy. Proc Natl Acad Sci USA. 2021;118(12):e2022410118. doi:10.1073/pnas.2022410118.
  • Lajoie MJ, Boyken SE, Salter AI, Bruffey J, Rajan A, Langan RA, Olshefsky A, Muhunthan V, Bick MJ, Gewe M, et al. Designed protein logic to target cells with precise combinations of surface antigens. Sci. 2020;369(6511):1637–43. doi:10.1126/science.aba6527.
  • Choe JH, Watchmaker PB, Simic MS, Gilbert RD, Li AW, Krasnow NA, Downey KM, Yu W, Carrera DA, Celli A, et al. SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma. Sci Transl Med. 2021;13(591):eabe7378. doi:10.1126/scitranslmed.abe7378.
  • Cho JH, Collins JJ, Wong WW. Universal chimeric antigen receptors for multiplexed and logical control of T cell responses. Cell. 2018;173(6):1426–38.e11. doi:10.1016/j.cell.2018.03.038.
  • Jan M, Scarfò I, Larson RC, Walker A, Schmidts A, Guirguis AA, Gasser JA, Słabicki M, Bouffard AA, Castano AP, 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.
  • Zhang R-Y, Wei D, Liu Z-K, Yong Y-L, Wei W, Zhang Z-Y, Lv J-J, Zhang Z, Chen Z-N, Bian H, et al. Doxycycline inducible chimeric antigen receptor T cells targeting CD147 for hepatocellular carcinoma therapy. Front Cell Dev Biol. 2019;7. doi:10.3389/fcell.2019.00233.
  • Li H-S, Wong NM, Tague E, Ngo JT, Khalil AS, Wong WW. High-performance multiplex drug-gated CAR circuits. Cancer Cell. 2022;40(11):1294–305.e4. doi:10.1016/j.ccell.2022.08.008.
  • 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.
  • Paszkiewicz PJ, Fräßle SP, Srivastava S, Sommermeyer D, Hudecek M, Drexler I, Sadelain M, Liu L, Jensen MC, Riddell SR, et al. Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia. J Clin Invest. 2016;126(11):4262–72. doi:10.1172/JCI84813.
  • Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K, Flutter B, Marin V, Marafioti T, Chakraverty R, Linch D, 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.
  • Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L, Ponzoni M, Rossini S, Mavilio F, Traversari C, et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Sci. 1997;276(5319):1719–24. doi:10.1126/science.276.5319.1719.
  • Di Stasi A, Tey S-K, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, Straathof K, Liu E, Durett AG, Grilley B, 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.
  • Huang Z, Wu Y, Allen ME, Pan Y, Kyriakakis P, Lu S, Chang Y-J, Wang X, Chien S, Wang Y, et al. Engineering light-controllable CAR T cells for cancer immunotherapy. Sci Adv. 2020;6(8):eaay9209. doi:10.1126/sciadv.aay9209.
  • Wu Y, Liu Y, Huang Z, Wang X, Jin Z, Li J, Limsakul P, Zhu L, Allen M, Pan Y, et al. Control of the activity of CAR-T cells within tumours via focused ultrasound. Nat Biomed Eng. 2021;5(11):1336–47. doi:10.1038/s41551-021-00779-w.
  • Kosti P, Opzoomer JW, Larios-Martinez KI, Henley-Smith R, Scudamore CL, Okesola M, Taher MYM, Davies DM, Muliaditan T, Larcombe-Young D, 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.
  • Greenshpan Y, Sharabi O, Ottolenghi A, Cahana A, Kundu K, Yegodayev K, Elkabets M, Gazit R, Porgador A. Synthetic promoters to induce immune-effectors into the tumor microenvironment. Commun Biol. 2021;4(1):143. doi:10.1038/s42003-021-01664-7.
  • Jones BS, Lamb LS, Goldman F, Di Stasi A. Improving the safety of cell therapy products by suicide gene transfer. Front Pharmacol. 2014;5. doi:10.3389/fphar.2014.00254.
  • Spencer DM, Wandless TJ, Schreiber SL, Crabtree GR. Controlling signal transduction with synthetic ligands. Science. 1993;262(5136):1019–24. doi:10.1126/science.7694365.
  • Clackson T, Yang W, Rozamus LW, Hatada M, Amara JF, Rollins CT, Stevenson LF, Magari SR, Wood SA, Courage NL, et al. Redesigning an FKBP–ligand interface to generate chemical dimerizers with novel specificity. Proc Natl Acad Sci USA. 1998;95(18):10437–42. doi:10.1073/pnas.95.18.10437.
  • Iuliucci JD, Oliver SD, Morley S, Ward C, Ward J, Dalgarno D, Clackson T, Berger HJ. Intravenous safety and pharmacokinetics of a novel Dimerizer drug, AP1903, in healthy volunteers. J Clin Pharmacol. 2001;41(8):870–9. doi:10.1177/00912700122010771.
  • Foster MC, Savoldo B, Lau W, Rubinos C, Grover N, Armistead P, Coghill J, Hagan RS, Morrison K, Buchanan FB, et al. Utility of a safety switch to abrogate CD19.CAR T-cell–associated neurotoxicity. Blood. 2021;137(23):3306–9. doi:10.1182/blood.2021010784.
  • Foster MC, Savoldo B, Lau W, Rubinos C, Grover NS, Armistead PM, Coghill JM, Jamieson KJ, Hagan R, Morrison JK, et al. Abrogation of immune effector cell neurotoxicity syndrome (ICANS) by rimiducid (RIM) in patients treated with CD19-specific chimeric antigen receptor modified T-cells (CAR-T) engineered with an inducible Caspase 9 (iC9 CAR.19)-clinical and pharmacodynamic correlates. Blood. 2022;140:7437–8.
  • Del Bufalo F, De Angelis B, Caruana I, Del Baldo G, De Ioris MA, Serra A, Mastronuzzi A, Cefalo MG, Pagliara D, Amicucci M, et al. GD2-CART01 for relapsed or refractory high-risk neuroblastoma. N Engl J Med. 2023;388(14):1284–95. doi:10.1056/NEJMoa2210859.