An ideal cancer vaccine should contain both strongly immunogenic cancer-specific antigen and potent adjuvant for stimulating robust cellular immunity which are pivotal for clearance of cancer cells. However, most of commercially available adjuvants such as aluminum phosphate gel cannot stimulate robust cellular immune response. In the current study, we reformed microscale aluminum phosphate gel adjuvant into nanoscale and fabricated CpG loaded and B16F10 tumor cell membrane coated aluminum phosphate nanoparticles (APMC). The resultant nano-vaccines showed a size of around 60 nm and a negative surface charge of -40 mV. Tumor cell membrane not only served as tumor antigens but also effectively improved the colloidal dispersion of aluminum phosphate nanoparticles. Subcutaneously injected APMC were efficiently drained to mouse lymph nodes, significantly increased co-uptake of tumor antigen and CpG by lymph node resident antigen presenting cells, promoted maturation of these cells and enhanced lysosomal antigen escape. After immunizing mice, they triggered robust cellular immunity, including potent IFN-γ+CD4+ T cells, IFN-γ+CD8+ T cells, cytotoxic T lymphocytes and cytokine excretion in spleen and lymph node cells. The elicited responses significantly suppressed tumor growth and prolonged survival of mice in both prophylactic and therapeutic melanoma models. This promising vaccine delivery system shows great potential to clinical transformation and can be further developed for personalized cancer vaccines.
Keywords: Aluminum phosphate nanoparticles; Cancer vaccine; Lymph node targeting; Tumor cell membrane.
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