Prostate Tumor Antigen Discovery: Development of a Novel Genetic Approach
Abstract
Rational approaches to successful prostate cancer immunotherapy requires fundamental knowledge of mechanisms whereby tumor antigens are acquired, processed, and immune responses generated. Extensive heterogeneity of MHC Class I and II molecules affords the human population broad immune protection against infectious diseases, however, creates restrictions for cancer immunotherapy. These restrictions center around antigenic determinants generated from potential tumor-associated antigens. This project seeks to determine candidate prostate tumor antigens as an approach to developing rational immunotherapy. One candidate protein for study is prostate specific antigen (PSA). We found CD4+ T-cell responses to PSA in some men with chronic prostatitis, a presumed autoimmune disorder. Methods for isolating antigen presenting cells (DCs) were developed that: (a) acquired antigen from apoptotic prostate cancer cell lines and induced T-cell responses in vitro; (b) acquired PSA and PSA/anti-PSA complexes and generated CD8+ and CD4+ T-cell responses in vitro. These results suggest that PSA/anti-PSA complexes may be an immunotherapeutic approach for prostate cancer. To be effective, "prostate cancer antigen" specific cytotoxic T-cells must recognize antigen presented in the context of HLA molecules on the tumor cells. We show that prostate cancer cell lines (except LNCaP) express antigen processing and transport genes that were upregulated by interferon-gamma.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADB256670
Entities
People
- Dean L. Mann
Organizations
- University of Maryland, Baltimore