Spleen‐targeted neoantigen DNA vaccine for personalized immunotherapy of hepatocellular carcinoma

Abstract

Neoantigens are emerging as attractive targets to develop personalized cancer vaccines, but their immunization efficacy is severely hampered by their restricted accessibility to lymphoid tissues where immune responses are initiated. Leveraging the capability of red blood cells (RBCs) to capture and present pathogens in peripheral blood to the antigen‐presenting cells (APCs) in spleen, we developed a RBC‐driven spleen targeting strategy to deliver DNA vaccine encoding hepatocellular carcinoma (HCC) neoantigen. The DNA vaccine‐encapsulating polymeric nanoparticles that were intentionally hitchhiked on the preisolated RBCs could preferentially accumulate in the spleen to promote the neoantigen expression by APCs, 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. Remarkably, when combined with anti‐PD‐1, the vaccine achieved complete tumor regression and generated a robust systemic immune response with long‐term tumor‐specific immunological memory, which thoroughly prevented tumor recurrence and spontaneous lung metastasis. This study offers a prospective strategy to develop personalized neoantigen vaccines for augmenting cancer immunotherapy efficiency in immune “cold” HCC.

Red blood cell derived nanocarrier drug delivery system: A promising strategy for tumor therapy

“…Notably, the vaccine achieved complete tumor regression in combination with anti‐PD1 and produced a robust systemic immune response with long‐term tumor‐specific immune memory. This strategy completely prevented tumor recurrence and spontaneous metastasis 54 …”

Nanomaterial Delivery Vehicles for the Development of Neoantigen Tumor Vaccines for Personalized Treatment

“…Combining immunosuppressive agents can improve the DNA vaccine effects, and neoantigen DNA vaccines utilize erythrocyte capture to target the spleen and inhibit the growth of hepatocellular carcinoma. The antitumor efficacy was increased even further when combined with anti-PD-1 inhibitors, resulting in a 75% regression of subcutaneous tumors and a complete regression of in situ tumors, prolonging survival [47].…”

New insights into red blood cells in tumor precision diagnosis and treatment

“…The combination with anti-PD-1 resulted in complete tumor ablation and induced a tumor-memory immune response. 129…”