Suppression of an epidermal growth factor receptor-hyperproducing tumor by an immunotoxin conjugate of gelonin and a monoclonal anti-epidermal growth factor receptor antibody.
An immunotoxin was made by conjugating a murine monoclonal antibody (B4G7) that recognizes the human epidermal growth factor (EGF) receptor with gelonin, a ribosome-inactivating protein. This B4G7-gelonin conjugate was shown to be specifically cytotoxic for EGF receptor-hyperproducing cells. The conjugate was tested in nude mice and shown to be capable of suppressing the growth of an EGF receptor-hyperproducing squamous carcinoma cell (A431) solid tumor. Nude mice bearing an A431 cell tumor that were given injections i.p. for 5 consecutive days with at least 10 micrograms of the conjugate showed significant suppression of tumor growth for about 7 days. On the other hand, an unconjugated mixture of B4G7 and gelonin showed no specific antitumor activity against the A431 cell tumor. The growth of an EGF receptor-deficient small cell lung cancer cell (H69) tumor was not suppressed by injection of the conjugate. No toxic effects were observed in histological examination of nontumorous tissues of mice treated with at least 250 micrograms of conjugate per mouse. These results suggest that the conjugate may be useful for targeting therapy to EGF receptor-hyperproducing squamous carcinoma.
Hirota
N
N
Research and Development Division, Iwasaki Electric Co., Ltd., Saitama-Ken, Japan.
Ueda
M
M
Ozawa
S
S
Abe
O
O
Shimizu
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D066246:ErbB Receptors / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010940:Plant Proteins / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1; D014407:Tumor Cells, Cultured; D014846:Vulvar Neoplasms / Q000473:pathology
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D066246:ErbB Receptors