This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hirota, N. Articles by Shimizu, N. Search for Related Content PubMed PubMed Citation Articles by Hirota, N. Articles by Shimizu, N.

Suppression of an Epidermal Growth Factor Receptor-hyperproducing Tumor by an Immunotoxin Conjugate of Gelonin and a Monoclonal Anti-Epidermal Growth Factor Receptor Antibody¹

Research and Development Division, Iwasaki Electric Co., Ltd., 1-20 Fujimi-cho, Gyoda-shi, Saitama-Ken 361 [N. H.], and Departments of Surgery [M. U., S. O., O. A.] and Molecular Biology [N. S.], Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan

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 µg 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 µg of conjugate per mouse. These results suggest that the conjugate may be useful for targeting therapy to EGF receptor-hyperproducing squamous carcinoma.

¹ This work was supported by a Grant-in-Aid from the Ministry of Education, Science, and Culture, Japan.

² To whom requests for reprints should be addressed, at Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan.

Received 4/ 4/89. Revised 7/27/89. Accepted 9/13/89.