Targeted therapies in B-cell lymphomas: the role of bispecific antibodies and CAR-T cells

Authors

Keywords:

B lymphomas, immunotherapy, bispecific antibodies, CAR-T cells

Abstract

B-cell lymphomas constitute a significant public health concern due to their prevalence and therapeutic complexity. In recent decades, the development of novel immunotherapeutic strategies has led to remarkable advances in their treatment, with bispecific antibodies and CAR-T cells emerging as innovative alternatives for patients with relapsed or refractory disease. This study aimed to characterize both therapeutic modalities through an updated literature review of scientific publications available in Spanish, English, and Portuguese. A total of 54 references retrieved from specialized databases were analyzed, allowing the identification of their main mechanisms of action, advantages, and clinical limitations. Bispecific antibodies promote the simultaneous activation of the immune response against specific tumor antigens, with mosunetuzumab, glofitamab, and epcoritamab being among the most widely used agents. CAR-T cell therapy, in contrast, is based on the genetic modification of T lymphocytes to recognize and eliminate malignant cells, with tisagenlecleucel, axicabtagene ciloleucel, and lisocabtagene maraleucel representing some of the currently available options. Although CAR-T therapy generally demonstrates greater clinical efficacy, it is also associated with increased toxicity and more complex implementation requirements. Overall, both strategies have transformed the management of B-cell lymphomas by providing more targeted and potentially less toxic treatments than conventional therapies, establishing themselves as key pillars of modern immunotherapy.

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References

Abou Dalle, I., Dulery, R., Moukalled, N., Ricard, L., Stocker, N., El-Cheikh, J., Mohty, M., & Bazarbachi, A. (2024). Bi- and tri-specific antibodies in non-Hodgkin lymphoma: Current data and perspectives. Blood Cancer Journal, 14(1), 23. https://doi.org/10.1038/s41408-024-00989-w

Abramson, J. S., Solomon, S. R., Arnason, J., Johnston, P. B., Glass, B., Bachanova, V., Ibrahimi, S., Mielke, S., Mutsaers, P., Hernandez-Ilizaliturri, F., Izutsu, K., Morschhauser, F., Lunning, M., Crotta, A., Montheard, S., Previtali, A., Ogasawara, K., Kamdar, M., & TRANSFORM Investigators. (2023). Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of the phase 3 TRANSFORM study. Blood, 141(14), 1675–1684. https://doi.org/10.1182/blood.2022018730

Barraclough, A., & Hawkes, E. A. (2023). Antibody and immunotherapy in diffuse large B-cell lymphoma. Seminars in Hematology, 60(5), 338–345. https://doi.org/10.1053/j.seminhematol.2023.11.001

Buske, C. (2022). Mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma. The Lancet Oncology, 23(8), 967–969. https://doi.org/10.1016/S1470-2045(22)00385-0

Chennapragada, S. S., & Ramadas, P. (2026). Bispecific antibody toxicity. StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK603709/

Dickinson, M. J., Carlo-Stella, C., Morschhauser, F., Bachy, E., Corradini, P., Iacoboni, G., Khan, C., Wróbel, T., Trněný, M., Wu, S.-J., Cartron, G., Hertzberg, M., Sureda, A., Perez-Callejo, D., Lundberg, L., Relf, J., Dixon, M., Clark, E., ... Hutchings, M. (2022). Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. The New England Journal of Medicine, 387(24), 2220–2231. https://doi.org/10.1056/NEJMoa2206913

Gajzer, D. C., & Fromm, J. R. (2025). Flow cytometry for B-cell non-Hodgkin and Hodgkin lymphomas. Cancers, 17(5), 814. https://doi.org/10.3390/cancers17050814

Guidi, L., Etessami, J., Valenza, C., Valdivia, A., Meric-Bernstam, F., Felip, E., & Curigliano, G. (2025). Bispecific antibodies in hematologic and solid tumors: Current landscape and therapeutic advances. American Society of Clinical Oncology Educational Book, 45(3), e473148. https://doi.org/10.1200/EDBK-25-473148

Gurumurthi, A., Westin, J., & Subklewe, M. (2023). The race is on: Bispecifics vs CAR T cells in B-cell lymphoma. Blood Advances, 7(19), 5713–5716. https://doi.org/10.1182/bloodadvances.2022009066

Jiang, M., Bennani, N. N., & Feldman, A. L. (2017). Lymphoma classification update: B-cell non-Hodgkin lymphomas. Expert Review of Hematology, 10(5), 405–415. https://doi.org/10.1080/17474086.2017.1318053

Justicia Lirio, P. (2024). Desarrollo de células CAR-T fisiológicas e inducibles de 4a generación con aplicación en inmunoterapia antitumoral [Tesis doctoral, Universidad de Granada].

Kearl, T. J., Furqan, F., & Shah, N. N. (2024). CAR T-cell therapy for B-cell lymphomas: Outcomes and resistance mechanisms. Cancer Metastasis Reviews, 44(1), 12. https://doi.org/10.1007/s10555-024-10228-0

Klein, C., Brinkmann, U., Reichert, J. M., & Kontermann, R. E. (2024). The present and future of bispecific antibodies for cancer therapy. Nature Reviews Drug Discovery, 23(4), 301–319. https://doi.org/10.1038/s41573-024-00896-6

Litvin, R., Mian, A., Ondrejka, S. L., & Hill, B. T. (2025). SOHO state of the art updates and next questions | High-grade B-cell lymphomas: Pathologic and molecular classification and therapeutic implications. Clinical Lymphoma, Myeloma & Leukemia, 25(12), 844–850. https://doi.org/10.1016/j.clml.2025.04.021

Maziarz, R. T., Bishop, M. R., Tam, C. S., Borchmann, P., Worel, N., McGuirk, J. P., Holte, H., Waller, E. K., Jaglowski, S., Andreadis, C., Foley, S. R., Westin, J. R., Fleury, I., Ho, P. J., Mielke, S., Teshima, T., Janakiram, M., Hsu, J., Izutsu, K., ... Schuster, S. J. (2026). Five-year analysis of the JULIET trial of tisagenlecleucel in patients with relapsed/refractory large B-cell lymphoma. Journal of Clinical Oncology, 44(2), 86–91. https://doi.org/10.1200/JCO-25-00507

Minson, A., Verner, E., Giri, P., Butler, J., Janowski, W., Cheah, C. Y., Ratnasingam, S., Wong, S. M., Ku, M., Hertzberg, M., Herbert, K., Hamad, N., Yannakou, C. K., Swain, F., Neeson, P., Steiner, T. M., Saghebi, J., Blombery, P., Hunter, S. M., ... Dickinson, M. J. (2025). Glofitamab combined with Pola-R-CHP or R-CHOP as first therapy in younger patients with high-risk large B-cell lymphoma: Results from the COALITION study. Journal of Clinical Oncology, 43(23), 2595–2605. https://doi.org/10.1200/JCO-25-00481

Moreta, V., & Rosero, D. (2025). Advances in immunotherapy for acute lymphoblastic leukemia: Integration of CAR-T cell therapies and other immunological strategies. BioNatura Journal: Ibero-American Journal of Biotechnology and Life Sciences, 2(1), 23. https://doi.org/10.70099/BJ/2025.02.01.15

Neelapu, S. S., Jacobson, C. A., Ghobadi, A., Miklos, D. B., Lekakis, L. J., Oluwole, O. O., Lin, Y., Braunschweig, I., Hill, B. T., Timmerman, J. M., Deol, A., Reagan, P. M., Stiff, P., Flinn, I. W., Farooq, U., Goy, A. H., McSweeney, P. A., Munoz, J., Siddiqi, T., ... Locke, F. L. (2023). Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood, 141(19), 2307–2315. https://doi.org/10.1182/blood.2022018893

Nizamuddin, I. A., & Bartlett, N. L. (2025). Bispecific antibodies in follicular lymphoma. Haematologica, 110(7), 1472–1482. https://doi.org/10.3324/haematol.2024.285245

Revuelta Gómez, S., Somoano Marfull, A., Sutil Berjón, R., Sánchez Gabin, A., Galante Mulki, M. J., Barrios López, M., Drake Pérez, M., & Marco de Lucas, E. (2024). Terapia con células CAR-T: Claves para un correcto diagnóstico de sus complicaciones en la urgencia. SERAM, 1(1). https://www.piper.espacio-seram.com/index.php/seram/article/view/9784

Sheth, V. S., & Gauthier, J. (2021). Taming the beast: CRS and ICANS after CAR T-cell therapy for ALL. Bone Marrow Transplantation, 56(3), 552–566. https://doi.org/10.1038/s41409-020-01134-4

Thieblemont, C., Karimi, Y. H., Ghesquieres, H., Cheah, C. Y., Clausen, M. R., Cunningham, D., Jurczak, W., Do, Y. R., Gasiorowski, R., Lewis, D. J., Kim, T. M., van der Poel, M., Poon, M. L., Feldman, T., Linton, K. M., Sureda, A., Hutchings, M., Dinh, M. H., Kilavuz, N., ... Lugtenburg, P. J. (2024). Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial. Leukemia, 38(12), 2653–2662. https://doi.org/10.1038/s41375-024-02410-8

U.S. Food and Drug Administration. (2023). FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-epcoritamab-bysp-relapsed-or-refractory-diffuse-large-b-cell

Vera Sepúlveda, C. L. (2023). Expresión de CD20 en linfocitos T con un receptor antigénico quimérico anti-CD19 para su selección o eliminación [Tesis doctoral, Universitat de Barcelona].

Weiss, J. M., & Phillips, T. J. (2024). Taking a BiTE out of lymphoma: Bispecific antibodies in B-cell non-Hodgkin lymphoma. Cancers, 16(9), 1724. https://doi.org/10.3390/cancers16091724

Westin, J. R., Kersten, M. J., Salles, G., Abramson, J. S., Schuster, S. J., Locke, F. L., & Andreadis, C. (2021). Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. American Journal of Hematology, 96(10), 1295–1312. https://doi.org/10.1002/ajh.26301

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Published

2026-06-30

Issue

Vol. 4 No. 3 (2026): Educación, salud e innovación para el desarrollo sostenible: perspectivas desde la investigación aplicada (julio-septiembre)

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Copyright (c) 2026 Liliana Teruel-Leyva, Leonardo Silva-dos Santos, Kevin Antonio Pérez-Vaca, Paula Andrea Vargas-Mendoza, Daniela Estefanía Gallardo-Ruiz, Gary Raúl Vaca-González

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