Induction of autoantibodies to syngeneic prostate-specific membrane antigen by xenogeneic vaccination Journal Article
| Authors: | Gregor, P. D.; Wolchok, J. D.; Turaga, V.; Latouche, J. B.; Sadelain, M.; Bacich, D.; Heston, W. D. W.; Houghton, A. N.; Scher, H. I. |
| Article Title: | Induction of autoantibodies to syngeneic prostate-specific membrane antigen by xenogeneic vaccination |
| Abstract: | Prostate-specific membrane antigen (PSMA) is a prototypical differentiation antigen expressed on normal and neoplastic prostate epithelial cells, and on the neovasculature of many solid tumors. Monoclonal antibodies specific for PSMA are in development as therapeutic agents. Methodologies to actively immunize against PSMA may be limited by immunologic ignorance and/or tolerance that restrict the response to self-antigens. Our studies have previously shown that xenogeneic immunization with DNA vaccines encoding melanosomal differentiation antigens induces immunity in a mouse melanoma model. Here we apply this approach to PSMA to establish proof of principle in a mouse model. Immunization with xenogeneic human PSMA protein or DNA induced antibodies to both human and mouse PSMA in mice. Monoclonal antibodies specific for mouse PSMA were generated to analyze antibody isotypes and specificity for native and denatured PSMA at the clonal level. Most antibodies recognized denatured PSMA, but C57BL/6 mice immunized with xenogeneic PSMA DNA followed by a final boost with xenogeneic PSMA protein yielded autoantibodies that reacted with native folded mouse PSMA. Monoclonal antibodies were used to confirm the expression of PSMA protein in normal mouse kidney. These results establish the basis for clinical trials to test PSMA DNA vaccines in patients with solid tumors that either express PSMA directly or that depend on normal endothelial cells expressing PSMA for their continued growth. © 2005 Wiley-Liss, Inc. |
| Keywords: | controlled study; human tissue; human cell; nonhuman; solid tumor; antigen expression; prostate specific antigen; animal cell; mouse; animals; mice; animal tissue; cancer immunotherapy; melanoma; gene expression profiling; embryo; animal experiment; animal model; cell differentiation; monoclonal antibody; prostate cancer; prostatic neoplasms; endothelial cells; immunological tolerance; kidney; immunotherapy; antibody response; antigen recognition; vaccination; prostate epithelium; autoantigen; tumor immunity; antibody specificity; dna vaccine; melanoma antigen; protein folding; tumor growth; disease models, animal; autoantibody; neovascularization (pathology); vaccines, dna; autoantibodies; antibody formation; glutamate carboxypeptidase ii; antigens, surface; immunization; antibodies, heterophile; freund adjuvant; antigen antibody reaction; psma; protein denaturation; dna vaccines; immune therapy |
| Journal Title: | International Journal of Cancer |
| Volume: | 116 |
| Issue: | 3 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2005-09-01 |
| Start Page: | 415 |
| End Page: | 421 |
| Language: | English |
| DOI: | 10.1002/ijc.21014 |
| PUBMED: | 15800947 |
| PROVIDER: | scopus |
| PMCID: | PMC1951508 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 30" - "Export Date: 24 October 2012" - "CODEN: IJCNA" - "Source: Scopus" |
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