Methods in molecular biology (Clifton, N.J.) · 2026
Clinical Development of T-Cell Bispecific Antibodies: Review, Challenges, and Prospective Solutions in Solid Tumor.
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Ogami Chika, Ishiguro Takahiro
Аннотация
T-cell engaging bispecific antibodies (T-BsAbs) have emerged as a promising approach in cancer immunotherapy. This review explores the clinical development of T-BsAbs in solid tumors, highlighting their unique mechanism of action, which involves the simultaneous binding to tumor-associated antigens and the CD3 T-cell receptor, thereby redirecting T cells to tumor cells and activating them in an antigen-dependent manner. Despite their success in hematological malignancies, T-BsAbs face significant challenges in solid tumors, including on- and off-target toxicities, the selection of appropriate tumor-associated antigens, and the complexity of the tumor microenvironment. Safety concerns, such as cytokine release syndrome (CRS) and on-target, off-tumor toxicities, are major obstacles that need to be addressed. Recent advancements offer potential solutions to these challenges. This review provides a comprehensive overview of the current state of T-BsAb development, discussing recent advances, ongoing clinical trials, and emerging strategies to enhance their efficacy and safety in solid tumor treatment.