In vivo T-cell ablation by a holo-immunotoxin directed at human CD3.
- 1 April 1992
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 89 (7) , 2585-2589
- https://doi.org/10.1073/pnas.89.7.2585
Abstract
We have evaluated the in vivo efficacy of anti-CD3-CRM9, a holo-immunotoxin constructed with a diphtheria toxin binding-site mutant. Eighty percent of established human T-cell subcutaneous tumors in nude mice completely regressed following intraperitoneal injection of immunotoxin at a dose set at half the minimum lethal dose assayed in toxin-sensitive animals. Similar regressions produced by a 137Cs source required a dose in excess of 500 cGy. The high degree of in vivo T-cell ablation produced by this immunotoxin is apparently due to maintenance of the toxin translocation function provided by CRM9 and a necessary intracellular routing function supplied by CD3. This immunotoxin may be useful in treating conditions caused by pathologic oligoclonal T-cell expansion such as graft-versus-host disease, autoimmune diseases, and possibly AIDS.Keywords
This publication has 33 references indexed in Scilit:
- Influence of endogenous Thy1.1 cells upon the efficacy of an anti-Thy1.1 antibody-diphtheria toxin conjugateBioconjugate Chemistry, 1991
- The Effect of Anti-Neoplastic Drugs on Murine Acquired Immunodeficiency SyndromeScience, 1991
- HIV-1 entry into quiescent primary lymphocytes: Molecular analysis reveals a labile, latent viral structureCell, 1990
- Engraftment of Immune-Deficient Mice with Human Hematopoietic Stem CellsScience, 1988
- Different Susceptibilities of Normal T Cells and T Cell Lines to ImmunotoxinsScandinavian Journal of Immunology, 1988
- Development of an Immunotoxin with in Vivo Efficacy for Murine SystemsAnnals of the New York Academy of Sciences, 1987
- Mutations in Diphtheria Toxin Separate Binding from Entry and Amplify Immunotoxin SelectivityScience, 1987
- GRAFT-VERSUS-HOST DISEASE PREVENTION IN ALLOGENEIC BONE MARROW TRANSPLANTATION FROM HISTOCOMPATIBLE SIBLINGS A PILOT STUDY USING IMMUNOTOXINS FOR T CELL DEPLETION OF DONOR BONE MARROWTransplantation, 1987
- TRANSMEMBRANE TRANSPORT OF DIPHTHERIA TOXIN, RELATED TOXINS, AND COLICINSAnnual Review of Biochemistry, 1986
- Distinctive functional characteristics of human „T”︁ lymphocytes defined by E rosetting or a monoclonal anti‐T cell antibodyEuropean Journal of Immunology, 1981