Off-The-Shelf Multivalent Nanoconjugate Cancer Vaccine Rescues Host Immune Response against Melanoma

Abstract

Tumor-associated antigen-based cancer vaccines suffer from limited clinical success compared to alternative immunotherapies in melanoma, an aggressive skin cancer with an immunosuppressive tumor microenvironment. The anti-tumor potential of a multivalent nanoconjugate cancer vaccine platform – a cross-linked star-shaped polyglutamate carrier (StCl) with marked lymphotropic character conjugated with melanoma-associated peptide antigens is evaluated through redox-responsive linkers. The co-delivery of melanoma-associated peptide antigens by the nanoconjugate platform induced significant effector immune responses in a mouse melanoma model. The nanoconjugate platform synergized with a PD-1 inhibitor to revert the immunosuppressive melanoma tumor microenvironment by improving cytotoxic T-cell infiltration, which prompted a superior anti-tumor effect with prolonged overall survival without acute organ toxicity. The antigen-specific anti-tumor immune response induced by the nanoconjugate platform is also validated in a melanoma patient-derived xenograft mouse model. A promising, versatile StCl-based platform is reported for generating off-the-shelf multivalent nanoconjugate cancer vaccines for the safe and efficient immunotherapeutic treatment of melanoma.