Cancer vaccine from intracellularly gelated tumor cells functionalized with CD47 blockage and damage-associated molecular pattern exposure.

Abstract

The effectiveness of whole tumor cell vaccines prepared by traditional inactivation methodology is often hindered by insufficient immunogenicity. Here, we report development of a cancer vaccine through the intracellular gelation of tumor cells, combined with CD47 blockade and damage-associated molecular pattern (DAMP) exposure, for effective tumor prevention and treatment. Intracellular hydrogelation preserves the morphology and antigenicity of tumor cells. CD47 blockade and DAMP exposure synergistically enhance the "eat me" signals and inhibit the "don't eat me" signals on tumor cells, significantly improving their immunogenicity. In the context of tumor prevention and treatment of pre-existing tumors, this vaccine polarizes CD4⁺ T cells toward a T_H1 phenotype, reduces regulatory T cells and T cell exhaustion, and elicits a robust tumor-antigen-specific T cell response. When combined with an immune checkpoint inhibitor, this vaccine demonstrates enhanced efficacy in eradicating established tumors. The successful application of this vaccine using ascites and subcutaneous tumor cells supports the feasibility of developing personalized whole tumor cell vaccines for diverse tumor types.