Off‐The‐Shelf Multivalent Nanoconjugate Cancer Vaccine Rescues Host Immune Response against Melanoma
Abstract
AbstractTumor‐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.
Article Details
Authors (20)
Liane IF Moura
Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Av. Prof. Gama Pinto Lisboa 1649‐003 Portugal
Alessio Malfanti
Polymer Therapeutics Lab Prince Felipe Research Center (CIPF) C/Eduardo Primo Yúfera 3 Valencia 46012 Spain
Ana I Matos
Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Av. Prof. Gama Pinto Lisboa 1649‐003 Portugal
Carina Peres
Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Av. Prof. Gama Pinto Lisboa 1649‐003 Portugal
Ana Armiñán
Polymer Therapeutics Lab Prince Felipe Research Center (CIPF) C/Eduardo Primo Yúfera 3 Valencia 46012 Spain
Aroa Duro‐Castaño
Polymer Therapeutics Lab Prince Felipe Research Center (CIPF) C/Eduardo Primo Yúfera 3 Valencia 46012 Spain
Inmaculada Conejos‐Sánchez
Polymer Therapeutics Lab Prince Felipe Research Center (CIPF) C/Eduardo Primo Yúfera 3 Valencia 46012 Spain
María Medel
Polymer Therapeutics Lab Prince Felipe Research Center (CIPF) C/Eduardo Primo Yúfera 3 Valencia 46012 Spain
Snežana Đorđević
Polymer Therapeutics Lab Prince Felipe Research Center (CIPF) C/Eduardo Primo Yúfera 3 Valencia 46012 Spain
Paula Carrascosa
Polymer Therapeutics Lab Prince Felipe Research Center (CIPF) C/Eduardo Primo Yúfera 3 Valencia 46012 Spain
Bárbara Carreira
Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Av. Prof. Gama Pinto Lisboa 1649‐003 Portugal
Rita C Acúrcio
Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Av. Prof. Gama Pinto Lisboa 1649‐003 Portugal
Helena Xavier‐Ferreira
i3S – Instituto de Investigação e Inovação em Saúde Medical Faculty of Porto Universidade do Porto Rua Alfredo Allen, 208 Porto 4200‐135 Portugal
Alberto Hernández‐Barranco
Microenvironment and Metastasis Laboratory Department of Molecular Oncology Spanish National Cancer Research Center (CNIO) C. de Melchor Fernández Almagro, 3 Madrid 28029 Spain
Elena Castellano
Microenvironment and Metastasis Laboratory Department of Molecular Oncology Spanish National Cancer Research Center (CNIO) C. de Melchor Fernández Almagro, 3 Madrid 28029 Spain
Esther Roselló
Department of Pathology Hospital General Universitario de Valencia Av. de les Tres Creus, 2, L'Olivereta Valencia 46014 Spain
José C. Machado
i3S – Instituto de Investigação e Inovação em Saúde Medical Faculty of Porto Universidade do Porto Rua Alfredo Allen, 208 Porto 4200‐135 Portugal
Héctor Peinado
María J. Vicent
Polymer Therapeutics Lab Prince Felipe Research Center (CIPF) C/Eduardo Primo Yúfera 3 Valencia 46012 Spain
Helena F. Florindo
Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy Universidade de Lisboa Av. Prof. Gama Pinto Lisboa 1649‐003 Portugal