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Recombinant Immunotoxins for the Treatment of Chemoresistant Hematologic Malignancies

Author(s): Robert J. Kreitman

Affiliation: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 37/5124b, 9000 Rockville Pike, Bethesda, MD 20892, USA.

Abstract:

Recombinant immunotoxins are proteins composed of fragments of monoclonal antibodies fused to truncated protein toxins. No agents of this class are approved yet for medical use, although a related molecule, denileukin diftitox, composed of interleukin-2 fused to truncated diphtheria toxin, is approved for relapsed/refractory cutaneous T-cell lymphoma. Recombinant immunotoxins which have been tested in patients with chemotherapy-pretreated hematologic malignancies include LMB-2 (anti-CD25), BL22 (CAT-3888, anti-CD22) and HA22 (CAT-8015, anti-CD22), each containing an Fv fragment fused to truncated Pseudomonas exotoxin. Major responses were observed with LMB-2 in adult T-cell leukemia, chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma, Hodgkins disease, and hairy cell leukemia (HCL). BL22 resulted in a high complete remission rate in patients with HCL, particularly those without excessive tumor burden. HA22, an improved version of BL22 with higher affinity to CD22, is now undergoing phase I testing in HCL, CLL, non-Hodgkins lymphoma, and pediatric acute lymphoblastic leukemia.

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Article Details

VOLUME: 15
ISSUE: 23
Page: [2652 - 2664]
Pages: 13
DOI: 10.2174/138161209788923949
Price: $58