The long-term goal of our continuing study is to identify prostate carcinoma-associated antigens using monoclonal antibodies (Mabs), and to assess the clinical application of these Mabs for diagnosis, prognosis, and therapy of prostate cancer. A major aim is to continue evaluation of the specificity of two Mabs, 83.21 and 6.2, and then to determine their clinical utility. We plan to achieve this aim by determining if these Mabs can be of use for detecting the antigens (83.21 and 6.2) in tissue sections, cytology specimens, and body fluids. We will continue to use the immunoperoxidase (IP) assay to determine the specificity of these Mabs with the aim of developing a useful immunohistopathological classification system. The detection of tumor cells in cytology specimens (aspiration biopsies of prostate tumors) will be determined by indirect immunofluorescence (IF) cytometry. A immunoradiometric assay will be developed to determine if the antigens are shed in serum or urine. Tissues, cytology specimens and body fluids, obtained before, during and after therapy, will be tested to determine the effect of therapy on antigen expression, how early the antigens can be detected, and if the Mabs have application for treatment monitoring and prognosis of the cancer patient. Another aim is to purify antigens 83.21 and 6.2, using affinity and lectin chromatography, for the purpose of producing Mabs to different epitopes expressed on these antigens. Such antibodies may enhance the sensitivity and specificity of the immunoassays for detecting these antigens in body fluids and tissues. The potential of these Mabs for radioimmunological imaging of prostate tumors will be evaluated in nude mice induced with prostate tumors. Because the heterogeneity of prostate tumor cell populations may necessitate the need for a panel of Mabs, we plan to continue to establich the specificities of Mabs produced from mouse/mouse fusion experiments, where prostate tumor tissue is used as the immunogen. These Mabs will be screened for reactivity against a panel of normal and malignant cell lines and tissues by radioimmunoassay, IF and IP. Those found to demonstrate restrictive reactivity to prostate tumors will be tested for clinical applicability. Mabs of the IgG isotype (especially IgG2a) will be evaluated for their potential to inhibit growth of tumors in nude mice. It is expected the experiments outlined in this grant proposal will yield a panel of well-characterized Mabs that will have clinical applicability.
