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 Leonard, J. E. Articles by Dillman, R. O. Search for Related Content PubMed PubMed Citation Articles by Leonard, J. E. Articles by Dillman, R. O.

Inhibition of Human T-Cell Tumor Growth by T101-Ricin A-Chain in an Athymic Mouse Model¹

University of California San Diego, Cancer Center, T-011, La Jolla 92093 [J. E. L.], Biotherapeutics, Inc., La Jolla 92037 [D. E. J., D. L. S., R. O. D.], and Departments of Medicine, Hematology/Oncology Sections, Veterans Administration Medical Center and Scripps Clinic and Research Foundation, La Jolla 92161 [R. O. D.], California

An immunotoxin prepared with the pan-T-cell, anti-CD5, antibody T101, and purified ricin A-chain (RTA) was selectively cytotoxic in vitro, inactivating protein synthesis in the human T-cell line MOLT-4 but not in the human B-cell line 8392. Modulation studies showed that the immunoconjugate was more rapidly cleared from the cell surface than unconjugated T101. Preclinical evaluation of T101-RTA was conducted in a human T-cell, athymic mouse model (Dillman et al., Cancer Res., 45: 5632–5636, 1985). Tumor-bearing mice received single i.p. injections of saline, T101, UPC-10 (irrelevant IgG2a), unconjugated RTA, an irrelevant conjugate, UPC-10-RTA, a mixture of T101 plus RTA, or T101-RTA. T101-RTA was the most effective reagent. Thirty animals given injections of 33 µg of T101 showed reductions in tumor growth (compared to tumor growth in animals receiving phosphate-buffered saline) but no complete regressions. No decrease in tumor growth was observed with UPC-10. Animals given 12 µg of free RTA exhibited reduced tumor growth but only one complete regression was observed; similar results were obtained with mice given 45 µg of UPC-10-RTA or a mixture of 33 µg of T101 plus 12 µg of RTA. Eleven complete regressions and 18 partial regressions were produced in the 46 animals given injections of 45 µg of T101-RTA and tumor growth was almost completely blocked. No toxicity was observed in any experimental arm. These results suggest that T101-RTA may be administered safely and with significant antitumor effect.

¹ This work was supported in part by New Investigator Research Award 1 R23 CA 35692 and USPHS Grant CA35692 from the National Cancer Institute (to J. E. L.), National Cancer Institute Program Project Grant 1 P01 CA37494, The Veterans Administration, and Biological Response Modifiers Program Grant NCI-CM-37613-64.

² To whom requests for reprints should be addressed, at IDEC Pharmaceuticals Corp., 11099 N. Torrey Pines Rd., La Jolla, CA 92037.

Received 7/ 9/87. Revised 4/15/88. Accepted 5/25/88.