Tumor-specific neoantigens can be highly immunogenic, but their identification for each patient and the production of personalized cancer vaccines can be time-consuming and prohibitively expensive. In contrast, tumor-associated antigens are widely expressed and suitable as an off the shelf immunotherapy. Here, we developed a PLGA-based nanoparticle vaccine that contains both the immunogenic cancer germline antigen NY-ESO-1 and an α-GalCer analog IMM60, as a novel iNKT cell agonist and dendritic cell transactivator. Three peptide sequences (85-111, 117-143, and 157-165) derived from immunodominant regions of NY-ESO-1 were selected. These peptides have a wide HLA coverage and were efficiently processed and presented by dendritic cells via various HLA subtypes. Co-delivery of IMM60 enhanced CD4 and CD8 T cell responses and antibody levels against NY-ESO-1 in vivo. Moreover, the nanoparticles have negligible systemic toxicity in high doses, and they could be produced according to GMP guidelines. Together, we demonstrated the feasibility of producing a PLGA-based nanovaccine containing immunogenic peptides and an iNKT cell agonist, that is activating DCs to induce antigen-specific T cell responses.

Aix Marseille Univ CNRS INSERM CIML Centre d'Immunologie de Marseille Luminy Marseille France

Department of Tumor Immunology Radboud University Medical Center Radboud Institute for Molecular Life Sciences Nijmegen Netherlands

Institute of Macromolecular Chemistry v v i Academy of Sciences of the Czech Republic Prague Czechia

Medical Research Council Human Immunology Unit Radcliffe Department of Medicine Weatherall Institute of Molecular Medicine University of Oxford Oxford United Kingdom

Oncode Institute Nijmegen Netherlands

TRON Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz gGmbH Mainz Germany

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