THE OBJECTIVE IS TO DEVELOP AN IN VITRO IMMUNIZATION SYSTEM TO PRODUCE HUMAN MONOCLONAL ANTIBODIES TO CELL SURFACE ANTIGENS OF HUMAN BREAST CARCINOMA, COLON CARCINOMA, AND MALIGNANT MELANOMA.

THE OBJECTIVE IS TO DEVELOP AN IN VITRO IMMUNIZATION SYSTEM TO PRODUCE HUMAN MONOCLONAL ANTIBODIES TO CELL SURFACE ANTIGENS OF HUMAN BREAST CARCINOMA, COLON CARCINOMA, AND MALIGNANT MELANOMA. HUMAN MONOCLONAL ANTIBODIES ARE DESIRABLE FOR A VARIETY OF REASONS, INCLUDING: A.THE MAJORITY OF ANTIBODIES PRODUCED BY RODENTS IMMUNIZED WITH HUMAN CELLS ARE AGAINST SPECIES-SPECIFIC RATHER THAN POLYMORPHIC DETERMINANTS, B.SPECIES-SPECIFIC CARBOHYDRATE PORTIONS OF IMMUNOGLOBULINS ARE IMPORTANT IN SEVERAL ANTIBODY EFFECTOR FUNCTIONS, ANDC.WHEN MURINE ANTIBODIES ARE USED THERAPEUTICALLY, IT IS LIKELY THAT THEIR ACTIVITY WILL BE NEUTRALIZED BY THE FORMATION OF HUMAN TUMOR-SENSITIZED B LYMPHOCYTES WILL BE GENERATED BY THIS IN VITRO SYSTEM AND FUSED WITH A NEWLY DESCRIBED HUMAN-MOUSE CELL LINE, SBC-H20, THAT EFFICIENTLY PRODUCES LONG-TERM STABLE HUMAN IMMUNOGLOBULIN SECRETING HYBRIDOMAS. A DETAILED STUDY OF THE IN VITRO IMMUNIZATION SYSTEM WILL BE PERFORMED IN PHASE I OF THIS PROPOSAL TO DETERMINE THE OPTIMUM TIME FOR COLLECTION OF B LYMPHOCYTES FOR FUSION. ANTIBODIES GENERATED BY THIS SYSTEM WILL BE CHARACTERIZED BY REACTIVITY TO PRIMARY TUMOR AND WITH OTHER ALLOGENEIC TUMOR CELLS USING FROZEN AND PARAFFIN SECTIONS, AND OTHER NORMAL TISSUE CONTROLS. THESE ANTIBODIES SHOULD ULTIMATELY BE USEFUL AS IN VIVO TUMOR-IMAGING REAGENTS AND POSSIBLY AS POTENTIAL THERAPEUTIC AGENTS IN THE TREATMENT OF THESE MALIGNANCIES.