影响T细胞双特异性抗体癌症免疫治疗疗效的因素及改进策略
Factors Affecting the Cancer Immunotherapeutic Efficacy of T Cell Bispecific Antibodies and Strategies for Improvement.
作者信息
Long Meixiao, Mims Alice S, Li Zihai
机构信息
Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
出版信息
Immunol Invest. 2022 Nov;51(8):2176-2214. doi: 10.1080/08820139.2022.2131569. Epub 2022 Oct 19.
T-cell bispecific antibodies (T-BsAbs) are a new class of cancer immunotherapy drugs that can simultaneously bind to tumor-associated antigens on target cells and to the CD3 subunit of the T-cell receptor (TCR) on T cells. In the last decade, numerous T-BsAbs have been developed for the treatment of both hematological malignancies and solid tumors. Among them, blinatumomab has been successfully used to treat CD19 positive malignancies and has been approved by the FDA as standard care for acute lymphoblastic leukemia (ALL). However, in many clinical scenarios, the efficacy of T-BsAbs remains unsatisfactory. To further improve T-BsAb therapy, it will be crucial to better understand the factors affecting treatment efficacy and the nature of the T-BsAb-induced immune response. Herein, we first review the studies on the potential mechanisms by which T-BsAbs activate T-cells and how they elicit efficient target killing despite suboptimal costimulatory support. We focus on analyzing reports from clinical trials and preclinical studies, and summarize the factors that have been identified to impact the efficacy of T-BsAbs. Lastly, we review current and propose new approaches to improve the clinical efficacy of T-BsAbs.
T细胞双特异性抗体(T-BsAbs)是一类新型的癌症免疫治疗药物,能够同时结合靶细胞上的肿瘤相关抗原以及T细胞上T细胞受体(TCR)的CD3亚基。在过去十年中,已经开发出多种T-BsAbs用于治疗血液系统恶性肿瘤和实体瘤。其中,blinatumomab已成功用于治疗CD19阳性恶性肿瘤,并已获美国食品药品监督管理局(FDA)批准作为急性淋巴细胞白血病(ALL)的标准治疗药物。然而,在许多临床情况下,T-BsAbs的疗效仍不尽人意。为了进一步改善T-BsAb治疗,更好地了解影响治疗效果的因素以及T-BsAb诱导的免疫反应的本质至关重要。在此,我们首先回顾关于T-BsAbs激活T细胞的潜在机制以及尽管共刺激支持不足但它们如何引发有效靶细胞杀伤的研究。我们着重分析临床试验和临床前研究的报告,并总结已确定的影响T-BsAbs疗效的因素。最后,我们回顾当前并提出新的方法以提高T-BsAbs的临床疗效。