Recombinant immunotoxins for the treatment of chemoresistant hematologic malignancies.

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, Hodgkin's 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-Hodgkin's lymphoma, and pediatric acute lymphoblastic leukemia.

• Authors: Robert J Kreitman
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 15 Issue 23 Pg. 2652-64 ( 2009) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 19689336 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Diphtheria Toxin
• Immunotoxins
• Leukocidins
• Pseudomonas aeruginosa Cytotoxins
• Recombinant Proteins
• Toxins, Biological

Topics

• Clinical Trials as Topic
• Diphtheria Toxin (pharmacology)
• Drug Discovery (methods)
• Drug Resistance, Neoplasm (drug effects, immunology)
• Hematologic Neoplasms (drug therapy)
• Humans
• Immunotoxins (therapeutic use)
• Leukocidins (pharmacology)
• Models, Biological
• Recombinant Proteins (biosynthesis, therapeutic use)
• Toxins, Biological (pharmacology)