Huang Wei-Qiang, You Wei, Zhu Ya-Qi, Gao Fan, Wu Zhi-Zhi, Chen Guang, Xiao Jun, Shao Qi, Wang Long-Hai, Nie Xuan, Zhang Ze, Hong Chun-Yan, You Ye-Zi
Department of Urology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Hefei National Research Centre for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
Nat Nanotechnol. 2025 Mar;20(3):451-462. doi: 10.1038/s41565-024-01826-8. Epub 2025 Jan 3.
Autophagosome cancer vaccines can promote cross-presentation of multiple tumour antigens and induce cross-reactive T cell responses. However, so far, there is no effective method for obtaining a highly immunogenic autophagosomal cancer vaccine because autophagosomes, once formed, quickly fuse with lysosomes and cannot easily escape from cells. Here we report a functional TiNX nanodot that caps the autophagosome membrane lipid phosphatidylinositol-4-phosphate, blocking the fusion of autophagosomes with lysosomes and producing stable nanodot-coated autophagosomes in tumours. The formed nanodot-coated autophagosomes can escape from cancer cells to lymph nodes, where they activate tumour-specific T cells. We show that our approach reduces tumour burden and provide long-term immune surveillance protection for cured mice. This work provides a method for the direct formation of personalized autophagosome-based cancer vaccines in vivo, offering a promising strategy for tumour treatment.
自噬体癌症疫苗可以促进多种肿瘤抗原的交叉呈递并诱导交叉反应性T细胞应答。然而,到目前为止,尚无有效的方法来获得高度免疫原性的自噬体癌症疫苗,因为自噬体一旦形成,就会迅速与溶酶体融合,且不易从细胞中逸出。在此,我们报告了一种功能性TiNX纳米点,它覆盖自噬体膜脂质磷脂酰肌醇-4-磷酸,阻断自噬体与溶酶体的融合,并在肿瘤中产生稳定的纳米点包被的自噬体。形成的纳米点包被的自噬体可以从癌细胞逃逸到淋巴结,在那里它们激活肿瘤特异性T细胞。我们表明,我们的方法减轻了肿瘤负担,并为治愈的小鼠提供了长期的免疫监视保护。这项工作提供了一种在体内直接形成个性化自噬体癌症疫苗的方法,为肿瘤治疗提供了一种有前景的策略。