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Cytotoxic Effects of Anti-CD5 Radioimmunotoxins on Human Tumors in Vitro and in a Nude Mouse Model¹

Department of Therapeutic Radiology, Section on Experimental Cancer Immunology [D. J. B., D. A. V.] and Department of Laboratory Medicine/Pathology [J. M. M.], University of Minnesota, Minneapolis, MN 55455; and the Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109-0010 [D. J. B., D. E. H.]

An immunoconjugate, consisting of both toxin and radionuclide on the same antibody molecule, was synthesized by cross-linking the phytotoxin ricin to the T101 monoclonal antibody recognizing the CD5 cluster expressed on normal and malignant T-cells. The hybrid molecule was then labeled with iodine-125 by an iodine monochloride procedure. This radioimmunotoxin (RIT), which selectively bound to the CD5-positive CEM human leukemia cell line, was selectively inhibitory to antigen-positive cells in protein synthesis inhibition assays. RIT was only 3.0–7.8-fold less toxic and was 1.1–1.6-fold slower than unlabeled immunotoxin in inhibiting protein synthesis. Because of the radionuclide moiety, the RIT also provided information related to biodistribution and pharmacokinetics. Four days following intratumoral injection, more than 125-fold greater activity was found in CEM tumors implanted in nude mice as compared to normal tissues. The mean blood half-life for RIT was 25.7 h and for radiolabeled antibody, 91.3 h. Intratumoral injections of RIT selectively induced regression of established CEM tumors. To our knowledge, these studies are the first to demonstrate that a single immunoconjugate can combine the advantages of both a catalytic toxin and radionuclide for cancer therapy.

¹ This work is part of a doctoral thesis by J. M. Manske to fulfill the requirements of the Graduate School of the University of Minnesota and is Center for Experimental Transplantation and Cancer Research publication no. 33. This work was supported in part by National Cancer Institute grants R01-CA-31618, R01-CA-43368, R01-CA-36725, and P01-CA-21737, American Cancer Society Grant IM-502, and the Minnesota Medical Foundation.

² To whom requests for reprints should be addressed, at Department of Therapeutic Radiology, Box 367 UMHC, Harvard Street at East River Road, University of Minnesota, Minneapolis, MN 55455.

³ Scholar of the Leukemia Society of America.

Received 4/11/88. Revised 8/31/88. Accepted 9/21/88.