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Keywords

Chimeric antigen receptor T-cells (CAR T cells), Acute lymphoblastic leukemia (ALL), Non-Hodgkin lymphoma (NHL)

Abstract

Chimeric Antigen Receptor T (CAR-T) cell therapy has emerged as a revolutionary treatment modality for hematologic malignancies, including acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL). This innovative approach involves the genetic engineering of a patient's own T lymphocytes to express chimeric antigen receptors (CARs), which enables these cells to specifically recognize and eliminate malignant cells expressing target antigens. Clinical trials have demonstrated remarkable efficacy, with significant rates of complete remission and durable responses observed in patients who have relapsed or are refractory to conventional therapies. As advancements in CAR technology continue, there is potential for expanding its application to other hematologic and solid tumors, offering hope for improved outcomes in cancer therapies. This article highlights the transformative impact of CAR-T cell therapy in hematologic malignancies and emphasizes the need for further investigation to enhance its safety and effectiveness.

References

  1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.

  2. Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol. 2006;6(10):715–727.

  3. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674.

    5. Jayaraman J, Mellody MP, Hou AJ, et al. CAR-T design: Elements and their synergistic function. EBioMedicine. 2020;58:102931.

  5. Ahmad U, Khan Z, Ualiyeva D, et al. Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review. Adv Cancer Biol Metastasis. 2022;4:100035.

  6. Bui TA, Mei H, Sang R, Ortega DG, Deng W. Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment. EBioMedicine. 2024;106:105266.

  7. Wagner DL, Fritsche E, Pulsipher MA, et al. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021;18(6):379–93.

  8. 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.

  9. Wang C, Wang J, Che S, Zhao H. CAR-T cell therapy for hematological malignancies: History, status and promise. Heliyon. 2023;9(11):e21776.

  10. 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.

  11. 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.

  12. Dreyling M, Fowler NH, Dickinson M, et al. Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update. Blood. 2024;143(17):1713–1725.

  13. 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.

  14. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640–654.

  15. Jacobson CA, Chavez JC, Sehgal AR, 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.

  16. 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.

  17. Shah BD, Ghobadi A, Oluwole OO, 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.

  18. Abramson JS, Palomba ML, Gordon LI, 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):839–852.

  19. Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as secondline treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294–2308.

  20. Siddiqi T, Maloney DG, Kenderian SS, et al. Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1–2 study. Lancet. 2023;402(10402):641–654.

  21. Morschhauser F, Dahiya S, Palomba ML, et al. Lisocabtagene maraleucel in follicular lymphoma: the phase 2 TRANSCEND FL study. Nat Med. 2024;30(8):2199–2207.

  22. Wang M, Siddiqi T, Gordon LI, et al. Lisocabtagene maraleucel in relapsed/refractory mantle cell lymphoma: Primary analysis of the mantle cell lymphoma cohort from TRANSCEND NHL 001, a phase I multicenter seamless design Study. J Clin Oncol. 2024;42(10):1146–57.

  23. Roddie C, Sandhu KS, Tholouli E, et al. Obecabtagene autoleucel in adults with B-cell acute lymphoblastic leukemia. N Engl J Med. 2024;391(23):2219–30.

  24. Munshi NC, Anderson LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705–716.

  25. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388(11):1002–1014.

  26. 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.

  27. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335–347.

  28. Laetsch TW, Maude SL, Rives S, et al. Three-year update of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia in the ELIANA trial. J Clin Oncol. 2023;41(9):1664–1669.

  29. Schuster SJ, Tam CS, Borchmann P, et al. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021;22(10):1403–1415.

  30. Neelapu SS, Jacobson CA, Ghobadi A, et al. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023;141(19):2307–2315.

  31. Neelapu SS, Chavez JC, Sehgal AR, et al. Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5). Blood. 2024;143(6):496–506.

  32. Wang M, Munoz J, Goy A, et al. Three-year follow-up of KTE-X19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the ZUMA-2 study. J Clin Oncol. 2023;41(3):555–567.

  33. Shah BD, Ghobadi A, Oluwole OO, et al. Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. J Hematol Oncol. 2022;15(1):170.

  34. Abramson JS, Palomba ML, Gordon LI, et al. Two-year followup of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2024;143(5):404–416.

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