Open AccessImmunotherapy of Tumors with α2-Macroglobulin-Antigen Complexes Pre-Formed In Vivo
Author(s) -
Sudesh Pawaria,
Laura E. Kropp,
Robert J. Binder
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0050365
Subject(s) - cancer immunotherapy , biology , antigen , immune system , heat shock protein , peptide , immunotherapy , t cell receptor , t cell , cross presentation , chaperone (clinical) , antigen presenting cell , microbiology and biotechnology , immunology , biochemistry , medicine , gene , pathology
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.