Abstract：
T-cell-engaging bispecific antibody (TCB) therapies have emerged as a promising immunotherapeutic approach, effectively redirecting effector T cells to selectively eliminate tumor cells. The therapeutic potential of TCBs has been well recognized, particularly with the approval of multiple TCBs in recent years for the treatment of hematologic malignancies as well as some solid tumors. However, TCBs encounter multiple challenges in treating solid tumors, such as on-target off-tumor toxicity, cytokine release syndrome (CRS), and T cell dysfunction within the immunosuppressive tumor microenvironment, all of which may impact their therapeutic efficacy. In this review, we summarize clinical data on TCBs for solid tumor treatment, highlight the challenges faced, and discuss potential solutions based on emerging strategies from current clinical and preclinical research. These solutions include TCB structural optimization, target selection, and combination strategies. This comprehensive analysis aims to guide the development of TCBs from design to clinical application, addressing the evolving landscape of cancer immunotherapy.
摘要：
T细胞接合双特异性抗体（TCB）疗法已成为一种有前途的免疫治疗方法，有效地重定向效应T细胞以选择性消除肿瘤细胞。TCB的治疗潜力已得到广泛认可，特别是随着近年来多种TCB被批准用于血液系统恶性肿瘤和一些实体瘤的治疗。然而,TCB在治疗实体肿瘤时遇到多重挑战，如靶点外肿瘤毒性，细胞因子释放综合征（CRS），免疫抑制肿瘤微环境中的T细胞功能障碍，所有这些都可能影响他们的治疗效果。在这次审查中,我们总结了TCB用于实体瘤治疗的临床数据，强调面临的挑战，并讨论基于当前临床和临床前研究的新兴策略的潜在解决方案。这些解决方案包括TCB结构优化，目标选择,和组合策略。这项综合分析旨在指导TCB从设计到临床应用的发展，解决癌症免疫疗法的演变格局。
