Spleen targeted neoantigen DNA vaccine for personalized immunotherapy of hepatocellular carcinoma. Mus musculus

We herein developed a RBC-driven spleen targeting strategy to deliver DNA vaccine encoding neoantigen of hepatocellular carcinoma. The DNA vaccine-encapsulating polymeric nanoparticles that were intentionally hitchhiked onto the surface of pre-isolated RBCs could preferentially accumulate in the spleen to promote the neoantigen expression by APCs after systemic administration, resulting in the burst of neoantigen specific T cell immunity to prevent tumorigenesis in a personalized manner, and slow down tumor growth in the established aggressively growing HCC tumor characterized by an immune cold microenvironment. More remarkably, this vaccination paradigm could combine with checkpoint blockade of anti-PD-1 to achieve complete tumor regression, and confer significantly prolonged survival of these mice. In addition, the cured mice could generate a robust systemic immune response with long-term tumor-specific immunological memory, which thoroughly prevented tumor re-challenge and spontaneous lung metastases. Overall, this study offers a prospective strategy to develop personalized neoantigen vaccines for augmenting cancer immunotherapy efficiency on immune cold HCC.