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Immunotherapy of tumors with α2-macroglobulin-antigen complexes pre-formed in vivo.
- Source :
- PLoS ONE, Vol 7, Iss 11, p e50365 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- The cell surface receptor CD91/LRP-1 binds to immunogenic heat shock proteins (HSP) and α(2)M ligands to elicit T cell immune responses. In order to generate specific immune responses, the peptides chaperoned by HSPs or α(2)M are cross-presented on MHC molecules to T cells. While the immunogenic HSPs naturally chaperone peptides within cells and can be purified as an intact HSP-peptide complex, the peptides have had to be complexed artificially to α(2)M in previous studies. Here, we show that immunogenic α(2)M-peptide complexes can be isolated from the blood of tumor-bearing mice without further experimental manipulation in vitro demonstrating the natural association of tumor antigens with α(2)M. The naturally formed immunogenic α(2)M-peptide complexes are effective in prophylaxis and therapy of cancer in mouse models. We investigate the mechanisms of cross-presentation of associated peptides and co-stimulation by APCs that interact with α(2)M. These data have implications for vaccine design in immunotherapy of cancer and infectious disease.
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5d825a645d249f3ada085552f0fd415
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pone.0050365