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Induction of prostate tumor-specific CD8+ cytotoxic T-lymphocytes in vitro using antigen-presenting cells pulsed with
1Dendreon Corporation, Mountain View, California 94043, USA. mvpeshwa@dendreon.com
Background:
Most strategies in cancer immunotherapy are aimed at the induction of a strong cellular immune response against the tumor. Particularly, CD8+ T lymphocytes have been proven in multiple animal models to be critical for the eradication of solid tumors.
Methods:
We used a population of peripheral blood-derived antigen-presenting cells (APC), containing dendritic cells (DC), to generate prostate tumor-specific CD8+ T cells. Selected peptides from prostatic acid phosphatase (PAP), a prostate tissue-specific antigen, were shown to bind HLA-A2. A high-affinity peptide was used to generate peptide-specific CD8+ cytolytic T lymphocytes (CTL) from the peripheral blood of healthy donors.
Results:
The obtained PAP-peptide-specific CTL lysed peptide-coated target cells, vaccinia-infected target cells, and HLA-A2-positive prostate-tumor cells in vitro in an antigen-specific manner.
Conclusions:
Our results indicate that CTL precursors to the PAP gene product exist and could be potentially recruited to elicit an antitumor response. Thus, PAP is a suitable antigen for inclusion in prostate cancer vaccines.