The challenges and future of CAR T-cells for treating Multiple Myeloma
DOI:
https://doi.org/10.47611/jsrhs.v13i2.6707Keywords:
Multiple Myeloma, Immunotherapy, CAR T-cellsAbstract
CAR T-cell therapy is a concept that modifies blood cells to fight against cancers. Studies have found that this hasn’t had long-term effects, and research has been conducted to find challenges that could cause this. Multiple different antigens are one of these challenges, as well as inefficiency in this method of therapy are challenge to this concept. There are many advancements that have been made that help resolve some of these challenges. Different generations of these CARs allow for stronger cells. These generations are different layers of protection that involve modifications to make the CARs more efficient. Dual-antigen specifically allows one CAR to target two different antigens, which could be present in the separate cells of the same cancer. NK-cell therapy is a different concept following the ideas of CAR T-cell therapy that could grow widely in the near future. This involves natural killer cells which are cells that are already programmed to kill these cells, making it unnecessary to modify them. This would also be much more efficient and has a lot of potential to become a commonly used treatment. These ideas were gathered through an in-depth exploration of CAR T-cell therapy for multiple myeloma discussing the current challenges and potential solutions within the field.
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Albinger, N., Hartmann, J., & Ullrich, E. (2021). Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany. Gene Therapy, 28, 1–15. https://doi.org/10.1038/s41434-021-00246-w
National Cancer Institute. (2022). CAR T Cells: Engineering Immune Cells to Treat Cancer. National Cancer Institute; Cancer.gov.
https://www.cancer.gov/about-cancer/treatment/research/car-t-cells
Fischer, L., Grieb, N., Uwe Platzbecker, Vladan Vučinić, & Merz, M. (2023). CAR T cell therapy in multiple myeloma, where are we now and where are we heading for? European Journal of Haematology. https://doi.org/10.1111/ejh.14051
Roex, G., Timmers, M., Wouters, K., Campillo-Davo, D., Flumens, D., Schroyens, W., Chu, Y., Berneman, Z. N., Lion, E., Luo, F., & Anguille, S. (2020). Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma. Journal of Hematology & Oncology, 13(1). https://doi.org/10.1186/s13045-020-01001-1
Ittershagen, S., Ericson, S. G., Lamis Eldjerou, Shojaee, A., Bleickardt, E., Patel, M., Taran, T., Oezlem Anak, Hall, C., Leung, M., Roccoberton, D., Salmon, F., Fuchs, M., Romanov, V., & Lebwohl, D. (2019). Industry’s Giant Leap Into Cellular Therapy: Catalyzing Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy. Current Hematologic Malignancy Reports, 14(1), 47–55. https://www.researchgate.net/publication/330523025_Industry's_Giant_Leap_Into_Cellular_Therapy_Catalyzing_Chimeric_Antigen_Receptor_T_Cell_CAR-T_Immunotherapy
Porter, D. L., Levine, B. L., Kalos, M., Bagg, A., & June, C. H. (2011). Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia. New England Journal of Medicine, 365(8), 725–733. https://doi.org/10.1056/nejmoa1103849
University of Pennsylvania and Novartis Form Alliance to Expand Use of Personalized T Cell Therapy for Cancer Patients - Penn Medicine. (n.d.). Www.pennmedicine.org. Retrieved November 12, 2023, from https://www.pennmedicine.org/news/news-releases/2012/august/university-of-pennsylvania-and
Rasche, L., Hudecek, M., & Einsele, H. (2020). What is the future of immunotherapy in MM? Blood. https://doi.org/10.1182/blood.2019004176
Smith, E. L., Harrington, K., Staehr, M., Masakayan, R., Jones, J., Long, T. J., Ng, K. Y., Ghoddusi, M., Purdon, T. J., Wang, X., Do, T., Pham, M. T., Brown, J. M., De Larrea, C. F., Olson, E., Peguero, E., Wang, P., Liu, H., Xu, Y., & Garrett-Thomson, S. C. (2019). GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Science Translational Medicine, 11(485), eaau7746. https://doi.org/10.1126/scitranslmed.aau7746
Bianchi, G., & Anderson, K. C. (2014). Understanding biology to tackle the disease: Multiple myeloma from bench to bedside, and back. CA: A Cancer Journal for Clinicians, 64(6), 422–444. https://doi.org/10.3322/caac.21252
Röllig, C., Knop, S., & Bornhäuser, M. (2015). Multiple myeloma. The Lancet, 385(9983), 2197–2208. https://doi.org/10.1016/s0140-6736(14)60493-1
Wu, C., Zhang, L., Brockman, Q. R., Zhan, F., & Chen, L. (2019). Chimeric antigen receptor T cell therapies for multiple myeloma. Journal of Hematology & Oncology, 12(1). https://doi.org/10.1186/s13045-019-0823-5
Hartmann, J., Schüßler‐Lenz, M., Bondanza, A., & Buchholz, C. J. (2017). Clinical development of CAR T cells—challenges and opportunities in translating innovative treatment concepts. EMBO Molecular Medicine, 9(9), 1183–1197. https://doi.org/10.15252/emmm.201607485
Danhof, S., Hudecek, M., & Smith, E. L. (2018). CARs and other T cell therapies for MM: The clinical experience. Best Practice & Research Clinical Haematology, 31(2), 147–157. https://doi.org/10.1016/j.beha.2018.03.002
Raje, N., Berdeja, J., Lin, Y., Siegel, D., Jagannath, S., Madduri, D., Liedtke, M., Rosenblatt, J., Maus, M. V., Turka, A., Lam, L.-P., Morgan, R. A., Friedman, K., Massaro, M., Wang, J., Russotti, G., Yang, Z., Campbell, T., Hege, K., & Petrocca, F. (2019). Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. New England Journal of Medicine, 380(18), 1726–1737. https://doi.org/10.1056/nejmoa1817226
Teoh, P. J., & Chng, W. J. (2021). CAR T-cell therapy in multiple myeloma: more room for improvement. Blood Cancer Journal, 11(4), 1–18. https://doi.org/10.1038/s41408-021-00469-5
Mikkilineni, L., & Kochenderfer, J. N. (2017). Chimeric antigen receptor T-cell therapies for multiple myeloma. Blood, 130(24), 2594–2602. https://doi.org/10.1182/blood-2017-06-793869
Mayo Foundation for Medical Education and Research. (2023, September 2). Multiple myeloma. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/multiple-myeloma/symptoms-causes/syc-20353378#:~:text=Overview,build%20up%20in%20bone%20marrow.
Szalat, R., & Munshi, N. C. (2019). Novel agents in multiple myeloma. Cancer journal (Sudbury, Mass.). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589825/#:~:text=In%20the%20last%20five%20years,CD38)%20and%20elotuzumab%20(targeting%20the
Hansen, D. K., Sidana, S., Peres, L. C., Colin Leitzinger, C., Shune, L., Shrewsbury, A., Gonzalez, R., Sborov, D. W., Wagner, C., Dima, D., Hashmi, H., Kocoglu, M. H., Atrash, S., Simmons, G., Kalariya, N., Ferreri, C., Afrough, A., Kansagra, A., Voorhees, P., Baz, R., … Patel, K. K. (2023). Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 41(11), 2087–2097. https://doi.org/10.1200/JCO.22.01365
Munshi, N. C., Anderson, L. D., Jr, Shah, N., Madduri, D., Berdeja, J., Lonial, S., Raje, N., Lin, Y., Siegel, D., Oriol, A., Moreau, P., Yakoub-Agha, I., Delforge, M., Cavo, M., Einsele, H., Goldschmidt, H., Weisel, K., Rambaldi, A., Reece, D., Petrocca, F., … San-Miguel, J. (2021). Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. The New England journal of medicine, 384(8), 705–716. https://doi.org/10.1056/NEJMoa2024850
Salomon Manier, Tiziano Ingegnere, Guillaume Escure, Chloé Prodhomme, Morgane Nudel, Suman Mitra, Thierry Facon, Current state and next-generation CAR-T cells in multiple myeloma, Blood Reviews, Volume 54, 2022, 100929, ISSN 0268-960X, https://doi.org/10.1016/j.blre.2022.100929.
Senju, H., Kumagai, A., Nakamura, Y., Yamaguchi, H., Nakatomi, K., Fukami, S., Shiraishi, K., Harada, Y., Nakamura, M., Okamura, H., Tanaka, Y., & Mukae, H. (2018). Effect of IL-18 on the Expansion and Phenotype of Human Natural Killer Cells: Application to Cancer Immunotherapy. International journal of biological sciences, 14(3), 331–340. https://doi.org/10.7150/ijbs.22809
Davis, J., McGann, M., Shockley, A., & Hashmi, H. (2022, May 26). Full article: Idecabtagene Vicleucel versus Ciltacabtagene Autoleucel ... Taylor and Francis Online. https://www.tandfonline.com/doi/full/10.1080/17474086.2022.2081147
Lee, H., Ahn, S., Maity, R., Leblay, N., Ziccheddu, B., Truger, M., Chojnacka, M., Cirrincione, A., Durante, M., Tilmont, R., Barakat, E., Poorebrahim, M., Sinha, S., McIntyre, J., M.Y. Chan, A., Wilson, H., Kyman, S., Krishnan, A., Landgren, O., … Bahlis, N. J. (2023, August 31). Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma. Nature News. https://www.nature.com/articles/s41591-023-02491-5
Reynolds, S. (2023, September). Engineering car T-cell therapy to overcome limitations. National Cancer Institute. https://www.cancer.gov/news-events/cancer-currents-blog/2023/car-t-cell-therapies-overcoming-limitations#:~:text=Other%20studies%20in%20mice%20have,can%20grow%20again%2C%E2%80%9D%20Dr.
Hawkins, E. R., D'Souza, R. R., & Klampatsa, A. (2021). Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy. Biologics: targets & therapy, 15, 95–105. https://doi.org/10.2147/BTT.S291768
Zhao, Z., & Sadelain, M. (2023, May 23). Car T cell design: Approaching the elusive and-gate. Nature News. https://www.nature.com/articles/s41422-023-00828-w#citeas
Xue, L., Yi, Y., Xu, Q., Wang, L., Yang, X., Zhang, Y., Hua, X., Chai, X., Yang, J., Chen, Y., Tao, G., Hu, B., & Wang, X. (2021, September 14). Chimeric antigen receptor T cells self-neutralizing IL6 storm in patients with hematologic malignancy. Nature News. https://www.nature.com/articles/s41421-021-00299-6
Zhao, Z., Shi, L., Zhang, W., Han, J., Zhang, S., Fu, Z., & Cai, J. (2017). CRISPR knock out of programmed cell death protein 1 enhances anti-tumor activity of cytotoxic T lymphocytes. Oncotarget, 9(4), 5208–5215. https://doi.org/10.18632/oncotarget.23730
Zhao, Zhilong, Shi, L., Zhang, W., Han, J., Zhang, S., Fu, Z., & Cai, J. (2017, December 27). CRISPR knock out of programmed cell death protein 1 enhances anti-tumor activity of cytotoxic T lymphocytes. Oncotarget. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797044/
Honikel, M. M., & Olejniczak, S. H. (2022, September 15). Co-stimulatory receptor signaling in car-T cells. MDPI. https://www.mdpi.com/2218-273X/12/9/1303
Pang, Zhaojun, et al. “Current Progress of CAR-NK Therapy in Cancer Treatment.” Cancers, vol. 14, no. 17, 2 Sept. 2022, p. 4318, https://doi.org/10.3390/cancers14174318. Accessed 17 Nov. 2022.
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