zhengguangmycin and Breast-Neoplasms

With fusion of human heteromyeloma cells SHM-D33 and B lymphocytes obtained from axillary lymph nodes of a patient suffering from breast carcinoma, one hybridoma cell line which secretes human monoclonal antibody CM-1 to breast carcinoma was established. The hybridoma cells have been secreting human IgM (lambda light chain) stably for over 5 years. The CM-1 concentration of the supernatant of cell culture is 38.5 micrograms per ml and is the ascites that of 2 mg per ml. The reactivity of CM-1 to normal human tissues and several kinds of tumors was examined with immunohistochemical staining. The results showed that the CM-1 reacted strongly to breast carcinoma and weakly to myxoadenocarcinoma of the esophagus. CM-1 did not react to normal tissues or other kinds of tumors, such as breast fibroadenoma, medullary carcinoma of the thyroid, etc. After injection of 131I-CM-1 into abdominal cavity of the mice bearing breast carcinoma, the image of xenografted carcinoma can be obviously distinguished from the background of normal tissues. The inhibitory effect on growth of breast cancer xenograft in nude mice was 95% for CM-1-PYM conjugate and 58% for free drug. The above results showed that the hybridom cell line CM-1 stably secreting antibody reacted specificaly with breast carcinoma and it might be useful as a drug carrier in therapy of patients with breast carcinoma.

Topics: Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Bleomycin; Breast Neoplasms; Female; Humans; Hybridomas; Immunotoxins; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation

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.

Topics: Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Bleomycin; Breast Neoplasms; Female; Humans; Immunotoxins; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Tumor Cells, Cultured