Recombinant fusion proteins for targeting dendritic cell subsets in therapeutic cancer vaccine.

Details

Serval ID
serval:BIB_67289CA04690
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Recombinant fusion proteins for targeting dendritic cell subsets in therapeutic cancer vaccine.
Journal
Methods in enzymology
Author(s)
Corgnac S., Botelho N.K., Donda A., Romero P.
ISSN
1557-7988 (Electronic)
ISSN-L
0076-6879
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
632
Pages
521-543
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Dendritic cells (DCs) are professional antigen-presenting cells, which are optimal for the priming of a T cell response against pathogens and tumors. Therefore, many efforts are made to develop therapeutic cancer vaccines which preferentially target the antigen to DC subsets. To this aim, we developed two types of recombinant fusion proteins, which favor antigen delivery to pro-inflammatory DCs as well as the crosstalk between specialized subpopulations of DCs. The first approach combines peptide/CpG vaccination with the recruitment of iNKT cells to the tumor site via CD1d-antitumor scFv fusion proteins. The second approach is targeting the tumor antigen to cross-presenting Xcr1 <sup>+</sup> DCs via a fusion protein made of Xcl1 fused to a synthetic long peptide followed by an IgG1 Fc fragment. Both strategies allow a potent tumor-specific CD8 T cell response associated with tumor regression or tumor growth delay depending on the model. In the case of iNKT cell activation, the strategy relies on a strong IL-12 release by splenic DCs, while in the second case, the T cell response is strictly dependent on the presence of Xcr1 <sup>+</sup> cross-presenting DCs.
Keywords
Animals, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/immunology, Cancer Vaccines/therapeutic use, Cross-Priming, Dendritic Cells/immunology, HEK293 Cells, Humans, Killer Cells, Natural/immunology, Mice, Inbred C57BL, Neoplasms/immunology, Neoplasms/therapy, Recombinant Fusion Proteins/immunology, Recombinant Fusion Proteins/therapeutic use, CD1d, CD8+ T cell, Cross-presenting DC, Recombinant fusion protein, Tumor vaccine, Xcl1, Xcr1+ DC, iNKT cell
Pubmed
Web of science
Create date
06/02/2020 18:53
Last modification date
04/04/2021 6:37
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