P22 virus-like particles as an effective antigen delivery nanoplatform for cancer immunotherapy.

ABSTRACT

As a new strategy for cancer immunotherapy, therapeutic cancer vaccines have been greatly improved in recent years. However, addressing the needs to quickly and efficiently elicit a high-intensity immune response against neoantigen peptides, especially to induce an effective cytotoxic lymphocyte (CTL) reaction, remain challenges in this field. In this study, virus-like particles (VLPs) derived from the phage P22 were adopted to load peptide antigens on the surface, to test whether VLP technology can be used as a platform for efficient peptide antigen delivery by therapeutic cancer vaccines. The B and T epitopes (OVAB peptide and OVAT peptide) of ovalbumin (OVA) were used here as model antigens and fused individually at the C terminus of the coat protein (CP), which allowed display on the surface of P22 particles to form two types of vaccine particles (VLP-OVAB and VLP-OVAT). Subsequent experiments showed that VLP-OVAB induced an antibody titer against the peptide antigen as high as 5.0 × 105 and that VLP-OVAT induced highly effective cross-presentation and then strongly activated a T epitope-specific CTL response. Mouse tumor model experiments showed that VLP-OVAT could significantly inhibit tumor growth by increasing the proportions of CD4+ T cells, CD8+ T cells and effector memory T cells (TEM cells) and lowering the proportion of myeloid-derived suppressor cells (MDSCs) among tumor-infiltrating lymphocytes and splenocytes. Compared with other chemically synthesized nanomaterials, VLPs have obvious advantages as vaccine carriers due to their clear chemical composition, fixed spatial structure, excellent biocompatibility, and relatively high potential for clinical translation. Therefore, this platform may lay a solid foundation for the design and preparation of personalized therapeutic vaccines based on neoantigen peptides.