Enhanced cytotoxicity in multiple myeloma via T cells armed with bispecific T cell engager targeting B-cell maturation antigen on cancer cells and CD3 on T cells
Issued Date
2024-12-25
Resource Type
ISSN
15675769
eISSN
18781705
Scopus ID
2-s2.0-85207596406
Journal Title
International Immunopharmacology
Volume
143
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Immunopharmacology Vol.143 (2024)
Suggested Citation
Supimon K., Sangsuwannukul T., Luangwattananun P., Yenchitsomanus P.t. Enhanced cytotoxicity in multiple myeloma via T cells armed with bispecific T cell engager targeting B-cell maturation antigen on cancer cells and CD3 on T cells. International Immunopharmacology Vol.143 (2024). doi:10.1016/j.intimp.2024.113480 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101909
Title
Enhanced cytotoxicity in multiple myeloma via T cells armed with bispecific T cell engager targeting B-cell maturation antigen on cancer cells and CD3 on T cells
Author's Affiliation
Corresponding Author(s)
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Abstract
Multiple myeloma (MM), a cancer of plasma cells, remains difficult to treat due to its incurability and high recurrence rates. Recent advancements in immunotherapies, such as CAR T cells, bispecific antibodies, and bispecific T cell engagers (BITEs) targeting B-cell maturation antigen (BCMA), have improved treatment options for relapsed and refractory MM (RRMM). However, these therapies face challenges, including complex manufacturing, high cost, and severe side effects. In this study, we developed a stable cell line that produces anti-BCMA × anti-CD3 BITEs and generated BITE-armed T cells (BATs) as a novel MM treatment approach. These αBCMA × αCD3 BATs specifically targeted BCMA-expressing cells, promoting T cell activation, proliferation, and cytotoxicity. BATs demonstrated superior cytotoxicity compared to unarmed T cells, likely due to enhanced antigen specificity and targeting efficiency, even at low effector-to-target ratios. The antitumor activity of BATs against BCMA-expressing cells was antigen-specific and dose-dependent. BATs also triggered T cell expansion and significant cytokine release (IL-2, TNF-α, IFN-γ) without increasing IL-6, suggesting a lower risk of cytokine release syndrome (CRS). Our findings indicate that BCMA-targeting BATs offer a promising and accessible therapeutic strategy for MM, with a simple, rapid, and cost-effective production process. These results support future development of BITE-armed T cells as a novel cancer treatment to enhance therapeutic outcomes for MM patients.