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Targeting Pseudomonas exotoxin to hematologic malignancies
1Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Malignant cells of hematopoietic origin often express a variety of different growth factor receptors and antigens on their surface, at levels much higher than normal cells. These malignant cells can be selectively targeted with Pseudomonas exotoxin (PE) derivatives directed by interleukins 2, 4 and 6, and by Fv fragments of monoclonal antibodies to interleukin 2 receptor (IL2R) subunits, CD22 and other antigens present on these cells. Anti-Tac(Fv)-PE38, a single-chain recombinant immunotoxin which targets cells bearing the IL2Ra, is furthest along in preclinical development and is being prepared for clinical testing in patients with IL2Ra-positive leukemia, lymphoma and Hodgkin's disease.