[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 mumol.L-1 and 4.0 mumol.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 < 0.05), respectively. CM1-PYM conjugate showed remarkable suppression 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 immunoconjugate composed of a human monoclonal antibody and pingyangmycin is highly effective and the conjugate may be useful in therapy for human breast cancer.
Wang
W G
WG
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing.
Wang
S H
SH
Xue
Y C
YC
Zhen
Y S
YS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D001761:Bleomycin; C021771:zhengguangmycin