北大团队巧施“特洛伊木马”行动，取得癌症疫苗新突破

Core Insights - The emergence of tumor immunotherapy, particularly PD-1/PD-L1 antibodies, has transformed cancer treatment, but over 60% of patients with non-small cell lung cancer do not respond to existing therapies, highlighting the challenge of "cold tumors" that evade immune detection [1][2] - A new study published in Nature by teams from Peking University and Shenzhen Bay Laboratory introduces a novel approach to reactivate "cold tumors" through a mechanism called "checkpoint degradation-coupled antigen presentation" [1][2] Group 1: Research Findings - The research team developed a dual-function chimeric molecule called iVAC that simultaneously achieves "immune checkpoint degradation" and "high-quality antigen delivery," effectively reprogramming cancer cells to present antigens [4][6] - iVAC molecules can activate antigen-specific CD8+ T cells, showing efficacy comparable to bone marrow-derived dendritic cells (BMDCs) in stimulating immune responses [7] - The study identified cytomegalovirus (CMV) antigens as a target for iVAC, leveraging the presence of dormant memory T cells in the human body that can be awakened to attack tumors [8][10] Group 2: Technological Innovations - The meTPD technology enables targeted degradation of membrane proteins, allowing cancer cells to present high-quality antigens, thus transforming them into effective vaccine carriers [3][6] - iVAC's design integrates three components: a covalent PD-L1 nanobody, a degradation moiety, and an immune peptide segment, facilitating a Trojan horse strategy to convert immune-suppressive cancer cells into immune system messengers [6][10] - The research indicates that iVAC can effectively activate memory T cells in various cancer patients, demonstrating significant potential for broader applications in cancer immunotherapy [8][10]