Immunotherapy of melanoma using TRP2 peptide-loaded biodegradable nanoparticles combined with poly-IC

Abstract Vaccination with tumor epitopes associated with MHC-I is an attractive approach directed at inducing tumor-specific CTLs. However, challenges remain in improving the therapeutic efficacy of peptide epitope vaccines, including the low immunogenicity of peptide epitopes and insufficient stimulation of innate immune components in vivo. Herein, we report an innovative strategy to overcome the limitations. The essential feature of this strategy is vaccination using tumor epitope-loaded biodegradable nanoparticles (NPs) in combination with poly-IC. Carboxylated NPs were prepared using poly(lactic-co-glycolic acid), covalently conjugated with anti-H-2K bmAb, and then attached with H-2K bmolecules. Native peptides associated with the H-2K bmolecules of H-2K b-attached NPs were exchanged with melanoma-specific peptide TRP2 (180–188). TRP2 peptide-loaded NPs in combination with poly-IC efficiently induced TRP2-specific CTLs when immunized into melanoma-bearing mice as well as normal mice. Accordingly, TRP2 peptide-loaded NPs in combination with poly-IC exerted significant anti-tumor activity in mice implanted with B16-F10 melanoma cells. In addition, TRP2 peptide-loaded NPs in combination with poly-IC exerted potent anti-metastatic activity in mice i.v. injected with B16-F10 melanoma cells. These findings show that TRP2 peptide-loaded NPs combined with poly-IC could be an effective means in treating melanoma via the induction of TRP2-specific CTLs.