In vivo engineering tumor cells to a universal ‘all-in-one’ cancer vaccine with full antigen spectrum [scRNA-Seq]

These tumor-derived UniCVac can directly activate both CD4+ and CD8+ T cells in vitro, independent of APCs. Additionally, their co-stimulation and T cell growth-stimulating capabilities result in superior CD4+ and CD8+ T cell activation and proliferation comparable to traditional APCs, with enhanced PI3K-AKT pathways activation. Single cell transcriptome analysis confirmed the similarity in cellular subtypes between UniCVac and traditional APCs activated T cells.

In mouse models, the UniCVac vaccination reprogramed the tumor microenvironment from immunosuppressive to immune-permissive, induced robust CD4+ and CD8+ T cell expansion in both preventive and therapeutic tumor models and achieved complete tumor regression in vivo. Our approach provides a platform for the development of universal cancer vaccines with full antigen spectrum coverage and the ability to directly activate both CD4+ and CD8+ T cells, offering potential combinatorial opportunities with existing T cell-based immunotherapies against cancer.