Off‐The‐Shelf Multivalent Nanoconjugate Cancer Vaccine Rescues Host Immune Response against Melanoma
Liane I.F. Moura, Alessio Malfanti, Ana I. Matos, Carina Peres, Ana Armiñán, Aroa Duro‐Castaño, Inmaculada Conejos‐Sánchez, María Medel, Snežana Đorđević, Paula Carrascosa, Bárbara Carreira, Rita C. Acúrcio, Helena Xavier‐Ferreira, Alberto Hernández‐Barranco, Elena Castellano, Esther Roselló‐Lletí, José Carlos Machado, Héctor Peinado, Marı́a J. Vicent, Helena F. Florindo
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.