Mechanizm działania terapii CAR-T oraz jej zastosowanie w leczeniu nowotworów hematologicznych
Słowa kluczowe:
Terapia CAR-T, nowotworyStreszczenie
Nowotwory, a szczególnie te złośliwe wciąż stanowią wyzwanie dla ciągle rozwijającej się terapii onkologicznej. Chemioterapia, radioterapia czy nawet leczenie chirurgiczne nadal nie zawsze jest skuteczne i daje możliwość wyleczenia pacjenta. W wyniku tego zaistniała potrzeba stworzenia nowej formy terapii, co zaowocowało rozwojem terapii komórkowej. W wielu badaniach dały one satysfakcjonujące wyniki, co pozwoliło na ich dalszy rozwój i poszerzenie zakresu ich zastosowania. Terapia CAR-T wykorzystująca specjalnie zmodyfikowane limfocyty T i chimeryczne receptory antygenowe (ang. chimeric antigen receptor, CAR) od wielu lat jest obiektem badań w immunoonkologii. Wykazała się ona bardzo dużą skutecznością i efektywnością w terapii chorych na nowotwory hematologiczne. Te przełomowe wyniki pozwoliły na wprowadzenia i zatwierdzenia terapii CAR-T jako metody terapeutycznej m.in. w leczeniu ostrej białaczki limfoblastycznej. Celem poniższej pracy jest przedstawienie mechanizmu działania komórek CAR-T w opisywanej terapii oraz przedstawienie aktualnych badań i doniesień o jej zastosowaniu w poszczególnych nowotworach hematologicznych. Oprócz wspomnianych zagadanień, prowadzona jest obecnie także ogromna liczba innych badań, których celem jest poszerzenie zakresu działalności i wykorzystania terapii CAR-T.
Bibliografia
Bao, C., et al., The Application of Nanobody in CAR-T Therapy. Biomolecules, 2021. 11(2).
Ewa Wrona, P.P., Nowoczesna immunoterapia nowotworów — historia terapii komórkami CAR-T. 2019.
Eshhar, Z., et al., Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A, 1993. 90(2): p. 720-4.
Jiang, J.L.a.G., The journey of CAR-T therapy in hematological malignancies. 2022.
June, C.H., et al., CAR T cell immunotherapy for human cancer. Science, 2018. 359(6382): p. 1361-1365.
Kochenderfer, J.N., et al., Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood, 2010. 116(20): p. 4099-102.
Sommermeyer, D., et al., Fully human CD19-specific chimeric antigen receptors for T-cell therapy. Leukemia, 2017. 31(10): p. 2191-2199.
Stephen J. Schuster, M.R.B., Constantine S. Tam 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. 2017.
Schuster, S.J., et al., Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med, 2019. 380(1): p. 45-56.
Yan, W., et al., Application of Chimeric Antigen Receptor T Cells in the Treatment of Hematological Malignancies. Biomed Res Int, 2020. 2020: p. 4241864.
Jogalekar, M.P., et al., CAR T-Cell-Based gene therapy for cancers: new perspectives, challenges, and clinical developments. Front Immunol, 2022. 13: p. 925985.
Ma, S., et al., Current Progress in CAR-T Cell Therapy for Solid Tumors. Int J Biol Sci, 2019. 15(12): p. 2548-2560.
Qin, X., et al., Recent advances in CAR-T cells therapy for colorectal cancer. Front Immunol, 2022. 13: p. 904137.
Han, D., et al., Current Progress in CAR-T Cell Therapy for Hematological Malignancies. J Cancer, 2021. 12(2): p. 326-334.
Hay, K.A. and C.J. Turtle, Chimeric Antigen Receptor (CAR) T Cells: Lessons Learned from Targeting of CD19 in B-Cell Malignancies. Drugs, 2017. 77(3): p. 237-245.
Davis, T.A., D.K. Czerwinski, and R. Levy, Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression. Clin Cancer Res, 1999. 5(3): p. 611-5.
Chen, W.C., et al., In vivo targeting of B-cell lymphoma with glycan ligands of CD22. Blood, 2010. 115(23): p. 4778-86.
Olejniczak, S.H., et al., A quantitative exploration of surface antigen expression in common B-cell malignancies using flow cytometry. Immunol Invest, 2006. 35(1): p. 93-114.
Yang, J., et al., Therapeutic potential and challenges of targeting receptor tyrosine kinase ROR1 with monoclonal antibodies in B-cell malignancies. PLoS One, 2011. 6(6): p. e21018.
Walter, R.B., et al., Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood, 2012. 119(26): p. 6198-208.
Marofi, F., et al., CAR T cells in solid tumors: challenges and opportunities. Stem Cell Res Ther, 2021. 12(1): p. 81.
Dufva, O., et al., Integrated drug profiling and CRISPR screening identify essential pathways for CAR T-cell cytotoxicity. Blood, 2020. 135(9): p. 597-609.
Singh, N., et al., Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction. Cancer Discov, 2020. 10(4): p. 552-567.
Benmebarek, M.R., et al., Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells. Int J Mol Sci, 2019. 20(6).
Miao, L., et al., A Bibliometric and Knowledge-Map Analysis of CAR-T Cells From 2009 to 2021. Front Immunol, 2022. 13: p. 840956.
Brentjens, R.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): p. 4817-28.
Yu, W.L. and Z.C. Hua, Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety-A Systematic Review with Meta-Analysis. Cancers (Basel), 2019. 11(1).
Kochenderfer, J.N., et al., B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood, 2012. 119(12): p. 2709-20.
Zhang, X., et al., CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges. Front Immunol, 2022. 13: p. 927153.
Davila, M.L. and M. Sadelain, Biology and clinical application of CAR T cells for B cell malignancies. Int J Hematol, 2016. 104(1): p. 6-17.
Davila, M.L., et al., Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med, 2014. 6(224): p. 224ra25.
Brentjens, R.J., et al., CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med, 2013. 5(177): p. 177ra38.
Maude, S.L., et al., Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med, 2014. 371(16): p. 1507-17.
Grupp, S.A., et al., Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med, 2013. 368(16): p. 1509-1518.
Lee, D.W., et al., T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet, 2015. 385(9967): p. 517-528.
Maude, S.L., et al., Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med, 2018. 378(5): p. 439-448.
Warzocha, K., Przewlekła białaczka limfocytowa. 2009.
Mewawalla, P. and S. Nathan, Role of allogeneic transplantation in patients with chronic lymphocytic leukemia in the era of novel therapies: a review. Ther Adv Hematol, 2014. 5(5): p. 139-52.
Turtle, C.J., S.R. Riddell, and D.G. Maloney, CD19-Targeted chimeric antigen receptor-modified T-cell immunotherapy for B-cell malignancies. Clin Pharmacol Ther, 2016. 100(3): p. 252-8.
Kochenderfer, J.N., et al., Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol, 2015. 33(6): p. 540-9.
Porter, D.L., et al., Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med, 2015. 7(303): p. 303ra139.
Singh, N., et al., CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia. Curr Treat Options Oncol, 2016. 17(6): p. 28.
Fraietta, J.A., et al., Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med, 2018. 24(5): p. 563-571.
Fraietta, J.A., et al., Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood, 2016. 127(9): p. 1117-27.
Oflazoglu, E., I.S. Grewal, and H. Gerber, Targeting CD30/CD30L in oncology and autoimmune and inflammatory diseases. Adv Exp Med Biol, 2009. 647: p. 174-85.
Savoldo, B., et al., Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. Blood, 2007. 110(7): p. 2620-30.
Hombach, A., et al., Characterization of a chimeric T-cell receptor with specificity for the Hodgkin's lymphoma-associated CD30 antigen. J Immunother, 1999. 22(6): p. 473-80.
Wang, C.M., et al., Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial. Clin Cancer Res, 2017. 23(5): p. 1156-1166.
Younes, A., et al., Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med, 2010. 363(19): p. 1812-21.
Ramos, C.A., H.E. Heslop, and M.K. Brenner, CAR-T Cell Therapy for Lymphoma. Annu Rev Med, 2016. 67: p. 165-83.
Smith, E.L., et al., BCMA-Targeted CAR T-cell Therapy plus Radiotherapy for the Treatment of Refractory Myeloma Reveals Potential Synergy. Cancer Immunol Res, 2019. 7(7): p. 1047-1053.
Atanackovic, D., et al., Chimeric Antigen Receptor (CAR) therapy for multiple myeloma. Br J Haematol, 2016. 172(5): p. 685-98.
Bo Guo, M.C., Qingwang Han, Fan Hui, Hanren Dai, Wenying Zhang, Yajing Zhang, Yao Wang, Hongli Zhu, Weidong Han, CD138-directed adoptive immunotherapy of chimeric antigen receptor (CAR)-modified T cells for multiple myeloma. 2016.
Carpenter, R.O., et al., B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res, 2013. 19(8): p. 2048-60.
Opublikowane
18 czerwca 2023
Prawa autorskie (c) 2023 Lidia Ziętek, Robert Kasza, Michał Janik, Jakub Staniszewski, Maciej Koźlik
Licencja
Utwór dostępny jest na licencji Creative Commons Uznanie autorstwa – Użycie niekomercyjne – Bez utworów zależnych 4.0 Międzynarodowe.
