Success in anticancer immune therapy relies on stimulation of tumor antigen-specific T lymphocytes and effective infiltration of the T cells into tumor tissue. Here, a therapeutic vaccine that promotes proliferation and tumor infiltration of antigen-specific T cells in both inflamed and noninflamed tumor types is described. The vaccine consists of STING agonist 2′3′-cGAMP, TLR9 ligand CpG, and tumor antigen peptides that are loaded into nanoporous microparticles (μGCVax). μGCVax is effective in inhibiting lung metastatic melanoma, primary breast cancer, and subcutaneous colorectal cancer in their respective murine models, including functional cure of HER2-positive breast cancer. Mechanistically, μGCVax potently stimulates type I interferon expression in dendritic cells, and promotes CD8⁺ and CD103⁺ dendritic cell maturation and migration to lymph nodes and other lymphatic tissues. Antitumor responses are dependent on TLR9 and interferon α/β receptor signaling, and to a less extent on STING signaling. These results demonstrate a high potential for μGCVax in mediating antitumor immunity in personalized cancer therapy.

中文翻译：

---

颗粒治疗性疫苗协同激活抗肿瘤免疫

抗癌免疫治疗的成功依赖于刺激肿瘤抗原特异性 T 淋巴细胞和 T 细胞有效浸润到肿瘤组织中。本文描述了一种治疗性疫苗，可促进炎症和非炎症肿瘤类型中抗原特异性 T 细胞的增殖和肿瘤浸润。该疫苗由 STING 激动剂 2'3'-cGAMP、TLR9 配体 CpG 和加载到纳米多孔微粒 ( μ GCVax) 中的肿瘤抗原肽组成。μ GCVax 在各自的小鼠模型中有效抑制肺转移性黑色素瘤、原发性乳腺癌和皮下结直肠癌，包括 HER2 阳性乳腺癌的功能性治愈。机械地，μGCVax 有效刺激 I 型干扰素在树突细胞中的表达，并促进 CD8 ⁺和 CD103 ⁺树突细胞成熟和迁移到淋巴结和其他淋巴组织。抗肿瘤反应依赖于 TLR9 和干扰素α / β受体信号传导，在较小程度上依赖于 STING 信号传导。这些结果表明μ GCVax 在个性化癌症治疗中介导抗肿瘤免疫方面具有很高的潜力。