Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.641703
Keywords
NY-ESO-1; iNKT cell; B cell epitope; peptide vaccine; IMM60; PLGA nanoparticle; CD8 T cell; CD4 T cell
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Funding
- Horizon 2020 project PRECIOUS (H2020-NMP-2015-two-stage) [686089]
- U.K. Medical Research Council
- Oxford Biomedical Research Center
- Cancer Research UK [C399/A2291]
- ERC Advanced grant ARTimmune [834618]
- NWO Spinoza award
- NWO-Vici [918.14.655]
- H2020 EU Grant PROCROP [635122]
- European Research Council (ERC) [834618] Funding Source: European Research Council (ERC)
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A PLGA-based nanoparticle vaccine containing immunogenic cancer germline antigen NY-ESO-1 and iNKT cell agonist was developed, which efficiently induced antigen-specific T cell responses in vivo without systemic toxicity at high doses.
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 alpha-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.
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