Autophagosomes coated in situ with nanodots act as personalized cancer vaccines

Abstract

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 Ti₂NX 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.