EFFECT OF THE CONJUGATE COMPOSED OF A HUMAN MONOCLONAL ANTIBODY AND PINGYANGMYCIN ON MAMMARY CANCER

To avoid or reduce the induction of human anti-mouse antibody reaction,it is important to use human antibody for the preparation of therapeutic immunoconjugate. CM1, a human monoclonal antibody directed against mammary cancer, was linked to pingyangmycin(PYM),an antitumor antibiotic identical to bleomycin A5 currently in clinical use, employing Dextran T-40 as an intermediate agent. As determined by clonogenic assay with mammary cancer CAMA cells, the IC₅₀ values for CM1-PYM conjugate and free PYM were 0.35 μmol·L^-1 and0μmol·L^-1,respectively. Mammary cancer CAMA was transplanted sc in nude mice. Peritumoral injection of CM1-PYM conjugate at doses of 1.25 mg·kg^-1 and 2.5 mg·kg^-1 inhibited the growth of CAMA xenograft by 86%and 95%(P<0.01), whereas the injection of equivalent doses of free PYM inhibited CAMA xenograft by 49%and 58%(P<.05),respectively. CM1-PYM conjugate showed remarkable suppresstion on CAMA xenograft and the inhibitory effect of CM1-PYM conjugate was much higher than that of free PYM, By histo-pathological examination ,no toxic changes were found in the heart, lung,liver,intestines,kidney,spleen and bone marrow of the CM1-PYM-or PYM-treated animals. These results suggest that local administration of the immunoconjugatecomposed of a human monoclonal antibody and pingyangmycin is highly effective and the conjugate may be useful in therapy for human breast cancer.