The proposed experiments are designed to generate monoclonal antibodies which will allow us to identify aspects of glial neoplasms which are pertinent to predicting clinical course, and which may aid in planning therapy. The antibodies may also prove useful as tools with which to understand malignant transformation, and as therapeutic reagents. We have in previous work generated a large panel of mouse monoclonal antibodies which bind to normal rodent astrocytes. We now propose to determine whether any of these antibodies to normal cell components bind selectively or disproportionately to epitopes present in human neoplasms. The panel of antibodies will be screened to detect antibodies which bind to cultured normal human astrocytes, and to cultured neoplastic astrocytes. The panel will also be screened for antibodies which bind to tumor cells in biopsies taken at the time of neurosurgery. It has been established by others that antibodies to normal cell constituents are powerful tools which allow one to recognize sub-types in tumors, and to correlate the tumor appearance with clinical behavior. Using techniques which have succeeded in generating antibodies in rodent tissue, we now plan to generate monoclonal antibodies which bind to epitopes expressed selectively by human glial neoplasms. We will immunize mice with plasmalemmal fractions from cultured normal human astrocytes, and the kill the responding lymphocytes with cyclophosphamide. Next, the same animals will be immunized with plasmalemmal fractions from neoplastic cells, which should elicit an immune response directed against epitopes expressed in neoplastic but not normal astrocytes. Such tumor-specific antibodies should prove an even more powerful approach to defining sub-types of human neoplasms, and correlating immunophenotype with clinical behavior. Further, such antibodies can be used as immunotherapeutic reagents. Finally, selective monoclonal antibodies may serve as starting points for cloning the genes whose expression is regulated during neoplastic transformation.
