title: Immunotherapy of tumors with α2-macroglobulin-antigen complexes pre-formed in vivo.
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.
authors.affiliation: Department of Rheumatology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Sudesh
authors.initials: S
authors.lastname: Pawaria
authors.forename: Laura E
authors.initials: LE
authors.lastname: Kropp
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Binder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000936:Antigen-Antibody Complex / Q000097:blood; D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D007114:Immunization; D007167:Immunotherapy; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D010766:Phosphorylation; D011973:Receptors, LDL / Q000097:blood / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D025521:Tumor Suppressor Proteins / Q000097:blood / Q000276:immunology; D023041:Xenograft Model Antitumor Assays; D000511:alpha-Macroglobulins / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D010455:Peptides; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins; D000511:alpha-Macroglobulins