Expression of human prostate-specific antigen (PSA) in a mouse tumor cell line reduces tumorigenicity and elicits PSA-specific cytotoxic T lymphocytes |
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Authors: | Chungwen Wei Eugene Storozynsky A J McAdam Kun-Yun Yeh Brian R Tilton Richard A Willis Richard K Barth R John Looney Edith M Lord J G Frelinger |
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Institution: | (1) Cancer Center Immunology Unit, Box 704, University of Rochester, Rochester, NY 14642, USA Fax: (716) 461-4019, US;(2) Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA, US;(3) Department of Medicine, University of Rochester, Rochester, NY 14642, USA, US |
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Abstract: | Human prostate-specific antigen (PSA) has a highly restricted tissue distribution. Its expression is essentially limited
to the epithelial cells of the prostate gland. Moreover, it continues to be synthesized by prostate carcinoma cells. This
makes PSA an attractive candidate for use as a target antigen in the immunotherapy of prostate cancer. As a first step in
characterizing the specific immune response to PSA and its potential use as a tumor-rejection antigen, we have incorporated
PSA into a well-established mouse tumor model. Line 1, a mouse lung carcinoma, and P815, a mouse mastocytoma, have been transfected
with the cDNA for human PSA. Immunization with a PSA-expressing tumor cell line demonstrated a memory response to PSA which
protected against subsequent challenge with PSA-expressing, but not wild-type, tumors. Tumor-infiltrating lymphocytes could
be isolated from PSA-expressing tumors grown in naive hosts and were specifically cytotoxic against a syngeneic cell line
that expressed PSA. Immunization with tumor cells resulted in the generation of primary and memory cytotoxic T lymphocytes
(CTL) specific for PSA. The isolation of PSA-specific CTL clones from immunized animals further demonstrated that PSA can
serve as a target antigen for antitumor CTL. The immunogenicity studies carried out in this mouse tumor model provide a rationale
for the design of methods to elicit PSA-specific cell-mediated immunity in humans.
Received: 4 April 1996 / Accepted: 31 May 1996 |
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Keywords: | Prostate-specific antigen Prostate adenocarcinoma T-cell-mediated immunity Immunotherapy |
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