《自然》：抗癌疫苗大突破！北大团队开发全新癌症疫苗，降解PD-L1同时给癌细胞添加抗原标签，让癌细胞变成抗原呈递细胞

Core Viewpoint - The emergence of immunotherapy has significantly transformed the field of anti-tumor treatment, but the response rates remain low due to the immunosuppressive tumor environment and insufficient tumor-specific cytotoxic T lymphocytes (CTLs) [1][7]. Group 1: iVAC Development - Researchers from Peking University and Shenzhen Bay Laboratory have developed a novel intratumoral vaccine chimera (iVAC) that utilizes endocytosis mechanisms to deliver antigen peptide segments into cancer cells, reprogramming them to present foreign antigens and promoting durable anti-tumor immunity [1][8]. - The iVAC can carry selectable antigens, with the study using cytomegalovirus (CMV)-derived antigens, which have shown strong immune responses in preclinical models [1][8]. Group 2: Technical Foundation - The technology behind iVAC is based on the GlueTAC platform, which was published by the same research team in 2021. GlueTAC targets membrane proteins for degradation, improving efficiency compared to traditional methods [4][10]. - GlueTAC consists of a covalent single-domain antibody that forms irreversible bonds with target membrane proteins and a cell-penetrating peptide that accelerates endocytosis and degradation [4][10]. Group 3: Mechanism and Efficacy - iVAC modifies cancer cells to behave like antigen-presenting cells (APCs) by loading them with foreign antigen peptides, which are processed and presented on the cell surface, enhancing their antigen presentation capabilities [5][11]. - In experiments with a poorly immunogenic B16 cell line, iVAC treatment significantly increased the expression of MHC-I molecules and upregulated antigen presentation-related genes, leading to reduced tumorigenicity [5][11]. - In humanized mouse models, intratumoral injection of iVAC significantly inhibited tumor growth, with all treated mice cured and showing no recurrence upon long-term observation [5][11]. Group 4: Clinical Potential - The CMV antigen used in iVAC is widely recognized by the human immune system, making it a promising candidate for inducing strong immune responses in various cancer patients [5][11]. - The iVAC approach may serve as a universal strategy for activating anti-tumor immunity in different patients [6][12].