A spectrum of monoclonal antibodies reactive with human mammary tumor cells.

Abstract

Splenic lymphocytes of mice, immunized with membrane-enriched fractions of metastatic human mammary carcinoma tissues, were fused with NS-1 non-Ig secreting murine myeloma cell line. This resulted in the generation of hybridoma cultures secreting Ig reactive in solid-phase radioimmunoassays with extracts of metastatic mammary carcinoma cells from involved livers but not with extracts of apparently normal human liver. As a result of further screening of Ig reactivities and double cloning of cultures, 11 monoclonal antibodies were chosen that demonstrated reactivities with human mammary tumor cells and not with apparently normal human tissues. These monoclonal antibodies could be placed into at least 5 major groups on the basis of their differential binding to the surface of various live human mammary tumor cells in culture, to extracts of mammary tumor tissues or to tissue sections of mammary tumor cells studied by the immunoperoxidase technique. Whereas a spectrum of reactivities to mammary tumors was observed with the 11 monoclonal antibodies, no reactivity was observed to apparently normal cells of the following human tissues: breast, lymph node, lung, skin, testis, kidney, thymus, bone marrow, spleen, uterus, thyroid, intestine, liver, bladder, tonsils, stomach, prostate and salivary gland. Several of the antibodies demonstrated a pancarcinoma reactivity, showing binding to selected non-breast carcinomas. None of the monoclonal antibodies showed binding to purified ferritin or carcinoembryonic antigen. Monoclonal antibodies of all 5 major groups demonstrated binding to human metastatic mammary carcinoma cells in axillary lymph nodes and at distal sites.