深圳湾实验室×北京大学合作最新Nature：陈鹏/席建忠合作开发全新癌症疫苗——瘤内疫苗嵌合体

Core Viewpoint - The article discusses a novel approach to cancer immunotherapy through the development of an intratumoral vaccination chimera (iVAC) that combines immune checkpoint degradation with high-quality antigen presentation, aiming to enhance anti-tumor immunity and overcome immune evasion by tumors [4][5][7]. Group 1: Mechanisms of Tumor Immune Evasion - Tumors evade immune surveillance through various mechanisms, including the overexpression of inhibitory checkpoint proteins and impaired antigen presentation [3]. - The lack or dysfunction of tumor-specific cytotoxic T lymphocytes (CTLs) limits the response rates to immune checkpoint blockade (ICB) therapies [3]. Group 2: Development of iVAC - The research team developed the iVAC, which covalently links PD-L1 degradation agents with immunogenic antigens, enabling the reprogramming of tumor cells into antigen-presenting cell-like states [5][7]. - iVAC induces strong tumor-killing effects by reactivating resident antigen-specific CD8+ T cells and reshaping the tumor microenvironment to promote durable tumor-specific immunity [5][7]. Group 3: Experimental Validation - The iVAC technology was validated using antigens derived from cytomegalovirus (CMV) to activate CMV-specific T cells targeting breast cancer in vitro, in humanized mouse models, and in patient-derived tumor models [7]. - This innovative strategy transforms tumor cells into allies of the immune system, paving the way for more effective cancer immunotherapies [7].