Bibliographic Details
Title: |
PLGA Nanoparticles Co-encapsulating NY-ESO-1 Peptides and IMM60 Induce Robust CD8 and CD4 T Cell and B Cell Responses. |
Authors: |
Dölen, Yusuf, Gileadi, Uzi, Chen, Ji-Li, Valente, Michael, Creemers, Jeroen H. A., Van Dinther, Eric A. W., van Riessen, N. Koen, Jäger, Eliezer, Hruby, Martin, Cerundolo, Vincenzo, Diken, Mustafa, Figdor, Carl G., de Vries, I. Jolanda M. |
Source: |
Frontiers in Immunology; 2/25/2021, Vol. 11, pN.PAG-N.PAG, 15p |
Subject Terms: |
T cells, B cells, PEPTIDES, DENDRITIC cells, AMINO acid sequence |
Abstract: |
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. [ABSTRACT FROM AUTHOR] |
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Database: |
Complementary Index |