Therapeutic murine monoclonal antibodies developed for individual cancer patients

Abstract

The purpose of this work was to create antibodies that are highly specific to epitopes on the surface of patient tumor cells that, when added together as a "cocktail," bind to greater than 99% of the patient's tumor cells. We describe the rationale and the methods used to develop new murine hybridomas that secrete monoclonal antibodies reactive with surface markers expressed on breast, lung, colon, kidney, islet cell, and miscellaneous carcinomas and melanoma. A rapid immunofluorescence method (cell concentration fluorescence immunoassay) is also described that has been developed to rapidly screen culture supernatants on viable patient tumor cells, tumor cell lines, or peripheral blood cells. We report the development of one breast, five colon, and three melanoma, three nephroma, and two pancreatic islet cell carcinoma antibodies. The breast antibody binds to 75% of the breast tumors tested thus far and to the same percentage of colon tumors as do the five colon antibodies, 77-85%. The melanoma antibodies described react with 90-100% of the melanoma and prostate cancers tested. The total process of creating the hybridomas and screening the antibodies for potential clinical usefulness has taken from 6 to 9 months to complete, including testing normal tissue reactivity by immunohistochemistry and production of gram quantities of monoclonal antibodies from ascites.