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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Recombinant Immunotoxins for the Treatment of Chemoresistant Hematologic Malignancies

Author(s): Robert J. Kreitman

Volume 15, Issue 23, 2009

Page: [2652 - 2664] Pages: 13

DOI: 10.2174/138161209788923949

Price: $65

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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