AUTOIMMUNITY TO TESTICULAR GERM CELL ONCOFETAL ANTIGENS

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It is well established that neoplastic tissues often express early differentiation antigens that are found in embryonic tissues. Recent studies by us and others provide evidence that certain types of tumors also express antigens that cross-react immunologically with antigens (possibly differentiation antigens) expressed by spermatozoa. We will perform additional studies to determine which types of tumors bear such cross-reacting antigens and whether tumor immunity is altered in individuals with antisperm immunity. In the first series of experiments, we will use cytotoxicity, agglutination, immunofluorescence, and radioimmunoassay techniques to screen sera from cancer patients and tumor-bearing mice for antibodies that react with spermatozoa or other testicular antigens. We will further characterize the cross-reactivity of antispermatozoal antibody from tumor-bearing or sperm-immune humans and mice by antigen absorption studies and with a blot technique in which antigens are reacted with antisera after slab gel electrophoresis. In a second series of experiments, we will use transplantable tumors, chemical carcinogens, and spontaneous tumor models to study tumorigenesis in mice with high titers of antisperm antibodies as a result of vasectomy or hyperimmunization with syngeneic sperm antigens. We will focus on the development of those types of tumors that were cross-reactive with sperm antigens in the serological tests. In the third phase of this study, we will use in vivo cell transfer (Winn assay) and in vitro cytotoxicity tests to further investigate cellular and humoral immunological mechanisms affecting tumor growth in sperm-immune individuals. We have recently reported an increased incidence of spontaneous tumors after vasectomy in mice and are currently investigating this effect. We are characterizing cross-reacting antigens on testicular germ cells and cancer cells and studying the immunosuppressive effects of sperm and seminal plasma. (AG)