2021年4月9日，公共实验技术中心免疫学技术平台在科技大楼13-1室举办了SCI论文报告会，研究生唐铭作了题目为“Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy”的报告。会议由公共实验技术中心免疫学技术平台主任袁青教授主持，平台师生24人参加了本次会议。
报告内容主要介绍了阻断程序性细胞死亡1（PD-1）检查点的单克隆抗体彻底改变了癌症免疫治疗。然而，许多主要肿瘤类型仍然对抗PD-1治疗无反应，即使在有反应的肿瘤类型中，大多数患者也不能产生持久的抗肿瘤免疫。文章中描述了另一类“共刺激双特异性”，它将TSA交叉连接到CD28（TSAxCD28）并与TSAxCD3双特异性合作。TSAxCD28双特异性在基因人源化免疫活性小鼠模型或灵长类动物中单独使用或与PD-1阻滞剂联合使用时显示出很少或没有毒性，因此可能提供一种耐受性良好且“现成”的PD-1免疫治疗组合方法，可显著提高抗肿瘤疗效。
在会议中，参会师生就相关内容进行了交流和探讨。此次报告紧紧围绕免疫学技术平台目前开展的科研方向，展示了最新研究前沿和动态；开拓了师生科研思路，为后续课题设计、课题开展提供了指导，同时也锻炼了师生SCI论文的阅读、分析、写作能力，浓厚了免疫学技术平台的学术氛围。
Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy
Monoclonal antibodies that block the programmed cell death 1 (PD-1) checkpoint have revolutionized cancer immunotherapy. However, many major tumor types remain unresponsive to anti-PD-1 therapy, and even among responsive tumor types, most of the patients do not develop durable antitumor immunity. It has been shown that bispecific antibodies activate T cells by cross-linking the TCR/CD3 complex with a tumor-specific antigen (TSA). The class of TSAxCD3 bispecific antibodies have generated exciting results in early clinical trials. We have recently described another class of "costimulatory bispecifics" that cross-link a TSA to CD28 (TSAxCD28) and cooperate with TSAxCD3 bispecifics. Here, we demonstrate that these TSAxCD28 bispecifics (one specific for prostate cancer and the other for epithelial tumors) can also synergize with the broader anti-PD-1 approach and endow responsiveness-as well as long-term immune memory-against tumors that otherwise do not respond to anti-PD-1 alone. Unlike CD28 superagonists, which broadly activate T cells and induce cytokine storm, TSAxCD28 bispecifics display little or no toxicity when used alone or in combination with a PD-1 blocker in genetically humanized immunocompetent mouse models or in primates and thus may provide a well-tolerated and "off the shelf" combination approach with PD-1 immunotherapy that can markedly enhance antitumor efficacy.
图/文 徐文峰
