Tumor Lysate-Loaded Lipid Hybrid Nanovaccine Collaborated with an Immune Checkpoint Antagonist for Combination Immunotherapy.

ABSTRACT

Cancer vaccines have shown great potential for treating different types of cancer. However, the application of vaccination still presents two major challenges. One is efficiency of antigen delivery, and the other is dealing with immune tolerance accompanied with tumor development. Lipid zinc phosphate hybrid nanoparticles (LZnP NPs) with a unique material structure can realize efficient delivery of antigens to dendritic cells (DCs) and also serve as an adjuvant to promote immune responses. Herein, ZnP NPs are introduced to load toll-like receptor 4 agonist (monophosphoryl lipid A) and B16F10 melanoma cell-derived tumor lysate (TLS) for vaccination. To regulate immune tolerance, the immune checkpoint antagonist, d-peptide antagonist (D PPA-1), is involved in treatment. TLS-loaded LZnP nanovaccine can efficiently prime DCs and induce cytotoxic T lymphocytes response. The explored combination treatment further exhibits the anticipated tumor inhibition on therapeutic and prophylactic melanoma models with extended survival time. It demonstrates the possibility to combine TLS-loaded LZnP nanovaccine with D PPA-1 against melanoma and provides support to optimize the combination treatment based on nanovaccine and immune checkpoint therapy.