Induction of prostate tumor-specific CD8+ cytotoxic T-lymphocytes in vitro using antigen-presenting cells pulsed with prostatic acid phosphatase peptide.
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.
Peshwa
M V
MV
Dendreon Corporation, Mountain View, California 94043, USA. mvpeshwa@dendreon.com
Shi
J D
JD
Ruegg
C
C
Laus
R
R
van Schooten
W C
WC
D000135:Acid Phosphatase / Q000737:chemistry / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011467:Prostate / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000276:immunology*
D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D000135:Acid Phosphatase