EXPRESSION OF HUMAN PROSTATE-SPECIFIC ANTIGEN (PSA) IN A MOUSE-TUMOR CELL-LINE REDUCES TUMORIGENICITY AND ELICITS PSA-SPECIFIC CYTOTOXIC T-LYMPHOCYTES

Human prostate-specific antigen (PSA) has a highly restricted tissue d istribution. Its expression is essentially limited to the epithelial c ells 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 i ts potential use as a tumor-rejection antigen, we have incorporated PS A into a well-established mouse tumor model. Line 1, a mouse lung carc inoma, and P815, a mouse mastocytoma, have been transfected with the c DNA for human PSA. Immunization with a PSA-expressing tumor cell line demonstrated a memory response to PSA which protected against subseque nt challenge with PSA-expressing, but not wild-type, tumors. Tumor-inf iltrating lymphocytes could be isolated from PSA-expressing tumors gro wn in naive hosts and were specifically cytotoxic against a syngeneic cell line that expressed PSA. Immunization with tumor cells resulted i n the generation of primary and memory cytotoxic T lymphocytes (CTL) s pecific for PSA. The isolation of PSA-specific CTL clones from PSA. Th e 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 prov ide a rationale for the design of methods to elicit PSA-specific cell- mediated immunity in humans.