STING Protein‐Based In Situ Vaccine Synergizes CD4+ T, CD8+ T, and NK Cells for Tumor Eradication

Yanpu He,Celestine Hong,Shengnan Huang, Justin A. Kaskow, Gil Covarrubias,Ivan S. Pires, James C. Sacane,Paula T. Hammond,Angela M. Belcher

Advanced Healthcare Materials(2023)

引用 0|浏览2
暂无评分
摘要
Abstract Stimulator of interferon genes (STING) signaling is a promising target in cancer immunotherapy, with many ongoing clinical studies in combination with immune checkpoint blockade (ICB). Existing STING‐based therapies largely focus on activating CD8 + T cell or NK cell‐mediated cytotoxicity, while the role of CD4 + T cells in STING signaling has yet to be extensively studied in vivo. Here, a distinct CD4‐mediated, protein‐based combination therapy of STING and ICB as an in situ vaccine, is reported. The treatment eliminates subcutaneous MC38 and YUMM1.7 tumors in 70–100% of mice and protected all cured mice against rechallenge. Mechanistic studies reveal a robust T H 1 polarization and suppression of T reg of CD4 + T cells, followed by an effective collaboration of CD4 + T, CD8 + T, and NK cells to eliminate tumors. Finally, the potential to overcome host STING deficiency by significantly decreasing MC38 tumor burden in STING KO mice is demonstrated, addressing the translational challenge for the 19% of human population with loss‐of‐function STING variants.
更多
查看译文
关键词
situ vaccine synergizes cd4<sup>+</sup>,nk cells,tumor eradication,cd8<sup>+</sup>
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络