Utilizing CRISPR to Improve the Ability of CAR T-cells to Treat Leukemia
DOI:
https://doi.org/10.58445/rars.4085Keywords:
Leukemia, CAR T-cell therapy, CRISPR, Gene editingAbstract
In 2025, there were over 66,000 cases of leukemia in the United States. Common treatments include chemotherapy, targeted drug therapies, and immunotherapies. Despite all of the current treatment options, leukemia has been responsible for over 23,000 deaths in 2025 alone. One form of immunotherapy called CAR T-cell therapy has recently shown great promise as a personalized treatment method for leukemia. However, CAR T-cell therapy can have severe side effects such as infections, potential for secondary cancers, tumor resistance, and autoimmune responses. Clustered regularly interspaced short palindromic repeats (CRISPR) has emerged as a new gene editing technology that has the potential to greatly improve CAR T-cell therapy, helping to reduce these limitations and minimize the side effects. In this review, I will discuss the application of CRISPR to improve the ability of CAR T-cell therapy to treat leukemia.
References
Amiri, M., Moaveni, A. K., Majidi Zolbin, M., Shademan, B., & Nourazarian, A. (2024). Optimizing cancer treatment: the synergistic potential of CAR-T cell therapy and CRISPR/Cas9. Frontiers in immunology, 15, 1462697. https://doi.org/10.3389/fimmu.2024.1462697
Caribou Biosciences, Inc.. (2025, June 11). A phase 1, multicenter, open-label study of CB-012, a CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy in patients with relapsed/refractory acute myeloid leukemia (AMpLify) (ClinicalTrials.gov Identifier: NCT06128044). https://clinicaltrials.gov/study/NCT06128044
Chiesa, R., Georgiadis, C., Rashed, H., Preece, R., Hardefeldt, P., Chu, J., Selvage, J., Mishra, A., Ahmed, B., Adams, S., Thomas, R., Gilmour, K., Etuk, A., Yallop, D., O'Connor, D., Qasim, W., & Base-Edited CAR T Group (2026). Universal Base-Edited CAR7 T Cells for T-Cell Acute Lymphoblastic Leukemia. The New England journal of medicine, 394(2), 152–165. https://doi.org/10.1056/NEJMoa2505478
Cleveland Clinic. (2022, May 18). Leukemia: Symptoms, signs, causes, types & treatment. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/4365-leukemia
Daver, N. G., Maiti, A., Sallman D. A., Roboz, G. J., Solh, M. M., Milano, F., Strickland, S. A., Eghtedar, A., Kanner, S. B., Ledergor, G., Marcy, D., Garner, E., Francica, B. J., Shaw, M., Bird, K., Rattan, J., Zudaire, E., Portella, S., Vachhani, P., Park, J. H. (2024). A first-in-human phase I, multicenter, open-label study of CB-012, a next-generation CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy for adults with relapsed/refractory acute myeloid leukemia (AMpLify). Journal of Clinical Oncology, 42(16_suppl), TPS6586. https://doi.org/10.1200/JCO.2024.42.16_suppl.TPS6586
Eyquem, J., Mansilla-Soto, J., Giavridis, T., van der Stegen, S. J., Hamieh, M., Cunanan, K. M., Odak, A., Gönen, M., & Sadelain, M. (2017). Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature, 543(7643), 113–117. https://doi.org/10.1038/nature21405
Francica, B., Garner, E., Namburi, S., Colgan, C., Fowler, T., Mutha, D., Aviles, A., Stanaway, M., Guo, R., An, Z., Kelly, E., Degagné, É., Kwong, G., Edwards, L., Jakes, E., Shaw, M., Schilling, B., Huynh, J., Luu, R., … Kanner, S. (2024). Preclinical evaluation of CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy, that exhibits specific and potent cytotoxicity in acute myeloid leukemia (AML) xenograft models. Cancer Research, 84(6 Suppl.), Abstract 6323. https://doi.org/10.1158/1538-7445.AM2024-6323
Hay, K. A., Hanafi, L. A., Li, D., Gust, J., Liles, W. C., Wurfel, M. M., López, J. A., Chen, J., Chung, D., Harju-Baker, S., Cherian, S., Chen, X., Riddell, S. R., Maloney, D. G., & Turtle, C. J. (2017). Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood, 130(21), 2295–2306. https://doi.org/10.1182/blood-2017-06-793141
Lonez, C., & Breman, E. (2024). Allogeneic CAR-T Therapy Technologies: Has the Promise Been Met?. Cells, 13(2), 146. https://doi.org/10.3390/cells13020146
Mayo Clinic. (2025, June 27). CAR-T cell therapy. Mayo Clinic. https://www.mayoclinic.org/tests-procedures/car-t-cell-therapy/about/pac-20585020
National Cancer Institute. (2025). Cancer Stat Facts: Leukemia. National Institutes of Health. https://seer.cancer.gov/statfacts/html/leuks.html
Ottaviano, G., Georgiadis, C., Gkazi, S. A., Syed, F., Zhan, H., Etuk, A., Preece, R., Chu, J., Kubat, A., Adams, S., Veys, P., Vora, A., Rao, K., Qasim, W., & TT52 CRISPR-CAR group (2022). Phase 1 clinical trial of CRISPR-engineered CAR19 universal T cells for treatment of children with refractory B cell leukemia. Science translational medicine, 14(668), eabq3010. https://doi.org/10.1126/scitranslmed.abq3010
Ragoonanan, D., Sheikh, I. N., Gupta, S., Khazal, S. J., Tewari, P., Petropoulos, D., Li, S., & Mahadeo, K. M. (2022). The Evolution of Chimeric Antigen Receptor T-Cell Therapy in Children, Adolescents and Young Adults with Acute Lymphoblastic Leukemia. Biomedicines, 10(9), 2286. https://doi.org/10.3390/biomedicines10092286
Rees, J. H. (2022). Management of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). In N. Kröger (Eds.) et. al., The EBMT/EHA CAR-T Cell Handbook. (pp. 141–145). Springer. https://doi.org/10.1007/978-3-030-94353-0_27
Roberts, R. (2025, September 18). CRISPR CAR-T cells: Edited T Cells Are Revolutionizing Cancer Treatment. Synthego. https://www.synthego.com/blog/car-t-crispr-cancer
Synthego. (n.d.). What Is CRISPR: The Ultimate Guide To CRISPR Mechanisms, Applications, Methods & More. Synthego. https://www.synthego.com/learn/crispr
Wang, X., Lai, S.-H., He, G.-C., Zhang, S., Zhang, X.-P., Deng, Y., Lei, M., Li, H., Hai, Y. (2025). Allogeneic CD19-directed CAR T-cell therapy derived from umbilical cord blood for relapsed acute lymphoblastic leukemia. Blood, 146(Supplement 1), 4116. https://doi.org/10.1182/blood-2025-4116
Wei, W., Chen, Z. N., & Wang, K. (2023). CRISPR/Cas9: A Powerful Strategy to Improve CAR-T Cell Persistence. International journal of molecular sciences, 24(15), 12317. https://doi.org/10.3390/ijms241512317
Yang, H., Ren, S., Yu, S., Pan, H., Li, T., Ge, S., Zhang, J., & Xia, N. (2020). Methods Favoring Homology-Directed Repair Choice in Response to CRISPR/Cas9 Induced-Double Strand Breaks. International journal of molecular sciences, 21(18), 6461. https://doi.org/10.3390/ijms21186461
Zhang, Y., Qin, D., Shou, A. C., Liu, Y., Wang, Y., & Zhou, L. (2023). Exploring CAR-T Cell Therapy Side Effects: Mechanisms and Management Strategies. Journal of clinical medicine, 12(19), 6124. https://doi.org/10.3390/jcm12196124
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