Individually Specified Drug Immunoconjugates in Cancer Treatment
Forty-three patients, including 13 patients with metastatic breast cancer, each received an individuallyspecified combination of either Adriamycin(24 patients) or mitomycin-C(19 patients) conjugated murine monoclonal ant ibodies. Tumors were typed using a panel of antibodies with both immunohistochemistry and flow cytometry. Cocktails composed of 2–6 antibodies were selected based on binding greater than 80% of the malignant cells in the biopsy specimen. These monoclonal antibody cocktails were drug conjugated and administered intravenously.
Seventeen out of twenty-four patients had reactions (fever, chills, pruritis and skin rash) to the administration of Adriamycin immunoconjugates, but these were tolerable in all but two patients. In several patients it was demonstrated that there was limited antigenic drift among various biopsies within the same patient over time. Up to 1 gram of Adriamycin and up to 5 grams of monoclonal antibody were administered. Two patients with breast carcinoma had depinite improvement in ulcerating skin lesions. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody which unpredictably caused hemopoietic depression.
Similar findings were noted in 19 patients with mitomycin-C conjugates. Thrombocytopenia at a 60mg dose of mitomycin-C in this schedule was dose limiting. Preliminary serological evidence suggests that the development of an IgM antibody which is specific against the mouse monoclonal antibody has the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C than Adriamycin treated patients.
KeywordsBreast Cancer Breast Carcinoma Murine Monoclonal Antibody Nude Mouse Xenograft Antibody Selection
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