Practical aspects of CAR-T cell therapy

Česká verzia

Authors: Mihályová Jana ^1,2; Jelínek Tomáš ^1,2; Kaščák Michal ^1,2; Benková Kateřina ^1,2; Uraš Juraj ^1,2; Demel Ivo ¹; Kořístek Zdeněk ^1,2; Hájek Roman ^1,2
Authors place of work: Klinika hematoonkologie FN Ostrava ¹; Klinika hematoonkologie LF OU ²
Published in the journal: Klin Onkol 2022; 35(1): 44-54
Category: Reviews
doi: https://doi.org/10.48095/ccko202244

Summary

Background: Chimeric antigen receptor (CAR) T cell therapy has been gradually building its position in the treatment of hematological malignancies. Currently, there are three types of autologous anti-CD19 CAR-T cells approved for the treatment of selected relapsed B cell non-Hodgkin’s lymphomas and acute B-lymphoblastic leukemia in the Czech Republic. Additional clinical trials are ongoing to evaluate CAR-T cell therapy that targets other tumor-specific antigens. It is expected that some of these CAR-T cells will be approved for the treatment of other hemato-oncological diagnoses in the near future. Manufacturing and management of CAR-T cell therapy have been optimized. European Society for Blood and Marrow Transplantation and American Society for Transplantation and Cellular Therapy have updated their recommendations for the management and treatment of early CAR-T cell toxicity based on valuable experience gained during several years. Nevertheless, late toxicity remains an issue. It is crucial for patients undergoing this highly specific therapy to stay in follow-up for several decades. Intensive research and development have been devoted to manufacturing new CAR constructs with higher efficacy and lesser toxicity. A significant improvement in the availability of this, otherwise very expensive treatment, is expected from universal allogeneic T cells that will express CAR binding to tumor-specific antigen. Purpose: This review is focused on the preparation and administration of autologous CAR-T lymphocytes.

Keywords:

immunotherapy – chimeric antigen receptor – chimeric antigen receptor T cells

Zdroje

1. Quesnel B. CAR T-cells: a John von Neumann legacy? Curr Res Transl Med 2018; 66 (2): 35–36. doi: 10.1016/j.retram.2018.04.002.

2. Cartellieri M, Bachmann M, Feldmann A et al. Chimeric antigen receptor-engineered T cells for immunotherapy of cancer. J Biomed Biotechnol 2010; 2010: 956304. doi: 10.1155/2010/956304.

3. Maus MV, Grupp SA, Porter DL et al. Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 2014; 123 (17): 2625–2635. doi: 10.1182/blood-2013-11-492231.

4. Šmída M. Chimeric antigen receptor T-cells – gene therapy of the future for malignant diseases? Klin Onkol 2015; 28 (Suppl 4): 4S44–4S47. doi: 10.14735/amko20154s44.

5. Jena B, Moyes JS, Huls H et al. Driving CAR-based T-cell therapy to success. Curr Hematol Malig Rep 2014; 9 (1): 50–56. doi: 10.1007/s11899-013-0197-7.

6. Chmielewski M, Abken H. TRUCKS, the fourth-generation CAR T cells: current developments and clinical translation. Adv Cell Gene Ther 2020; 3 (3): e84. doi: 10.1002/acg2.84.

7. Kagoya Y, Tanaka S, Guo T et al. A novel chimeric antigen receptor containing a JAK–STAT signaling domain mediates superior antitumor effects. Nat Med 2018; 24 (3): 352–359. doi: 10.1038/nm.4478.

8. Ramakrishnan A, Ardeshna KM, Batlevi CL. Phase 1 Alexander study of AUTO3, the first CD19/22 dual targeting CAR T cell therapy, with pembrolizumab in patients with relapsed/refractory (r/r) DLBCL. J Clin Oncol 2020; 38 (Suppl 15): 8001. doi: 10.1200/JCO.2020.38.15_suppl.8001.

9. Ruella M, Barrett DM, Kenderian SS et al. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J Clin Invest 2016; 126 (10): 3814–3826. doi: 10.1172/JCI87366.

10. Yongxian H, Zhou Y, Zhang M et al. The safety and efficacy of a CRISPR/Cas9-engineered universal CAR-T cell product (CTA101) in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Blood 2020; 136 (Suppl 1): 52. doi: 10.1182/blood-2020-142262.

11. Mailankody S, Matous JV, Liedtke M et al. Universal: an allogeneic first-in-human study of the anti-bcma ALLO-715 and the anti-CD52 ALLO-647 in relapsed/refractory multiple myeloma. Blood 2020; 136 (Suppl 1): 24–25. doi: 10.1182/blood-2020-140641.

12. Yakoub-Agha I, Chabannon C, Bader P et al. Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica 2020; 105 (2): 297–316. doi: 10.3324/haematol.2019.229781.

13. Lee DW, Santomasso BD, Locke FL et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 2019; 25 (4): 625–638. doi: 10.1016/j.bbmt.2018.12.758.

14. Schuster SJ, Bishop MR, Tam CS et al. Primary analysis of Juliet: a global, pivotal, phase 2 trial of CTL019 in adult patients with relapsed or refractory diffuse large B-cell lymphoma. Blood 2017; 130 (1): 577–577. doi: 10.1182/blood.V130.Suppl_1.577.577.

15. Maude SL, Laetsch TW, Buechner J et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 2018; 378 (5): 439–448. doi: 10.1056/NEJMoa1709866.

16. Neelapu SS, Locke FL, Bartlett NL et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 2017; 377 (26): 2531–2544. doi: 10.1056/NEJMoa1707447.

17. Wang M, Munoz J, Goy A et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2020; 382 (14): 1331–1342. doi: 10.1056/NEJMoa1914347.

18. Lin Y, Noopur SR, Berdeja JG et al. Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in patients with relapsed and refractory multiple myeloma: updated results from phase 1 CRB-401 study. Blood 2020; 136 (Suppl 1): 26–27. doi: 10.1182/blood-2020-134324.

19. Berdeja JG, Madduri D, Usmani SZ et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet 2021; 398 (10297): 314-324. doi: 10.1016/S0140-6736 (21) 00 933-8.

20. Tyagarajan S, Spencer T, Smith J. Optimizing CAR-T cell manufacturing processes during pivotal clinical trials. Mol Ther Methods Clin Dev 2019; 16: 136–144. doi: 10.1016/ j.omtm.2019.11.018.

21. Gattinoni L, Finkelstein SE, Klebanoff CA et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med 2005; 202 (7): 907–912. doi: 10.1084/jem.20050732.

22. Hirayama AV, Gauthier J, Hay KA et al. The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells. Blood 2019; 133 (17): 1876–1887. doi: 10.1182/blood-2018-11-887067.

23. Neelapu SS. CAR-T efficacy: is conditioning the key? Blood 2019; 133 (17): 1799–1800. doi: 10.1182/blood-2019-03-900928.

24. Frey N, Porter D. Cytokine release syndrome with chimeric antigen receptor T cell therapy. Biol Blood Marrow Transplant 2019; 25 (4): e123–e127. doi: 10.1016/ j.bbmt.2018.12.756.

25. Gauthier J, Turtle CJ. Insights into cytokine release syndrome and neurotoxicity after CD19-specific CAR-T cell therapy. Curr Res Transl Med 2018; 66 (2): 50–52. doi: 10.1016/j.retram.2018.03.003.

26. Maude SL, Frey N, Shaw PA et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014; 371 (16): 1507–1517. doi: 10.1056/ NEJMoa1407222.

27. Hay KA, Hanafi L-A, Li D et al. Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood 2017; 130 (21): 2295–2306. doi: 10.1182/blood-2017-06-793141.

28. Schuster SJ, Bishop MR, Tam CS et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 2019; 380 (1): 45–56. doi: 10.1056/NEJMoa1804980.

29. Hill JA, Li D, Hay KA et al. Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood 2018; 131 (1): 121–130. doi: 10.1182/blood-2017-07-793760.

30. Strati P, Nastoupil LJ, Fayad LE et al. Safety of CAR T-cell therapy in patients with B-cell lymphoma and chronic hepatitis B or C virus infection. Blood 2019; 133 (26): 2800–2802. doi: 10.1182/blood.2019000888.

31. Majhail NS, Rizzo JD, Lee SJ et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Biol Blood Marrow Transplant 2012; 18 (3): 348–371. doi: 10.1016/j.bbmt.2011.12.519.

32. Minagawa K, Al-Obaidi M, Di Stasi A. Generation of suicide gene-modified chimeric antigen receptor-redirected T-cells for cancer immunotherapy. Methods Mol Biol 2019; 1895: 57–73. doi: 10.1007/978-1-4939-89 22-5_5.

33. Cherkassky L, Morello A, Villena-Vargas J et al. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Invest 2016; 126 (8): 3130–3144. doi: 10.1172/JCI83092.

34. Li S, Siriwon N, Zhang X et al. Enhanced cancer immunotherapy by chimeric antigen receptor-modified T cells engineered to secrete checkpoint inhibitors. Clin Cancer Res 2017; 23 (22): 6982–6992. doi: 10.1158/1078-0432.CCR-17-0867.

35. Liu X, Ranganathan R, Jiang S et al. A chimeric switch-receptor targeting PD1 augments the efficacy of second generation CAR T-cells in advanced solid tumors. Cancer Res 2016; 76 (6): 1578–1590. doi: 10.1158/0008-5472.CAN-15-2524.

36. Suarez ER, Chang DK, Sun J et al. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model. Oncotarget 2016; 7 (23): 34341–34355. doi: 10.18632/oncotarget.9114.

37. Georgiadis C, Preece R, Nickolay L et al. Long terminal repeat CRISPR-CAR-coupled “universal” T cells mediate potent anti-leukemic effects. Mol Ther 2018; 26 (5): 1215–1227. doi: 10.1016/j.ymthe.2018.02.025.

38. Torikai H, Reik A, Liu P-Q et al. A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR. Blood 2012; 119 (24): 5697–5705. doi: 10.1182/blood-2012-01-405365.

39. 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.

40. Urbanska K, Lanitis E, Poussin M et al. A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer Res 2012; 72 (7): 1844–1852. doi: 10.1158/0008-5472.CAN-11-3890.

41. Caimi P, Sharma A, Rojas P et al. CAR-T therapy for lymphoma with prophylactic tocilizumab: decreased rates of severe cytokine release syndrome without excessive neurologic toxicity. Blood 2020; 136 (Suppl 1): 30–31. doi: 10.1182/blood-2020-143114.

42. Kansagra, AJ, Frey NV, Bar M et al. Clinical utilization of chimeric antigen receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL) – an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT). Bone Marrow Transplant 2019; 54 (11): 1868–1880. doi: 10.1038/s41409-019-0451-2.

43. Korell F, Laier S, Sauer S et al. Current challenges in providing good leukapheresis products for manufacturing of CAR-T cells for patients with relapsed/refractory NHL or ALL. Cells 2020; 19 (5): 1225. doi: 10.3390/cells9051225.