Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; Jecho Laboratories, Inc., Frederick, MD 21704, USA.
Int Immunopharmacol. 2024 Sep 10;138:112609. doi: 10.1016/j.intimp.2024.112609. Epub 2024 Jul 6.
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.
T 细胞结合双特异性抗体（TCB）疗法作为一种有前途的免疫治疗方法已经出现，能够有效地将效应 T 细胞重新定向以选择性地消除肿瘤细胞。TCB 的治疗潜力已得到广泛认可，特别是近年来已批准多种 TCB 用于治疗血液系统恶性肿瘤和一些实体瘤。然而，TCB 在治疗实体瘤时遇到了多个挑战，例如针对目标的脱靶毒性、细胞因子释放综合征（CRS）以及免疫抑制肿瘤微环境中的 T 细胞功能障碍，这些都可能影响其治疗效果。在这篇综述中，我们总结了 TCB 在实体瘤治疗中的临床数据，重点介绍了面临的挑战，并根据当前临床和临床前研究中的新策略讨论了潜在的解决方案。这些解决方案包括 TCB 结构优化、靶标选择和联合策略。这一全面分析旨在指导 TCB 从设计到临床应用的发展，应对癌症免疫治疗的不断发展。
