HUMAN MONOCLONAL-ANTIBODY DEVELOPED AGAINST OVARIAN-CANCER CELL-SURFACE ANTIGEN

Background. Murine monoclonal antibodies (MoAb) potentially can be use d in the radioimmunodetection and radioimmunotherapy of cancer. Howeve r, the administration of these radiopharmaceuticals to humans often le ads to induction of human anti-murine antibodies (HAMA). HAMA has many disadvantages, which could decrease efficacy of the murine MoAb. The purpose of this work was to produce human monoclonal antibody against a human ovarian cancer cell surface antigen (OCCSA), which was not pre sent in normal ovarian cells. This 200-kilodalton OCCSA also was used in the present study for characterizing the human monoclonal antibody. Methods. Human monoclonal antibodies were produced in vitro by fusion of mutant myeloma cells, selected from GM1500, with human lymphoid ce lls immunized in vitro with purified OCCSA. The human monoclonal antib ody was characterized using the following techniques: sodium dodecyl s ulfate-polyacrylamide gel electrophoresis (SDS-PAGE), native-PAGE, Wes tern blotting followed by protein-A gold staining, immunodiffusion ass ays, and fluorescent antibody assays. Results. Human monoclonal antibo dy, TC5 (immunoglobulin G1), was produced and purified. It was found t o be specific for ovarian cancer, while also reacting with an early st age breast cancer. TC5 did not react with any normal (i.e., nonneoplas tic) cells of the ovary, uterus, cervix, endocervix, or fallopian tube , nor did it react with normal lung, heart, pancreas, liver, or breast tissue.Conclusion. Human-human hybridomas produced human monoclonal a ntibody against OCCSA. The human monoclonal antibody, TC5, was specifi c for ovarian and breast cancer. TC5 did not react with any normal tis sue tested. Future work will focus on the in vivo characterization of the human monoclonal antibody, after labeling with radionuclides. Canc er 1994; 73:1098-104.