经靶向肿瘤细胞 B 细胞成熟抗原和 T 细胞 CD3 的双特异性 T 细胞衔接器武装的 T 细胞增强多发性骨髓瘤细胞毒性

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 BCMA CD3 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- , IFN- ) 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.