Recombinant immunotoxins for the treatment of chemoresistant hematologic malignancies

Curr Pharm Des. 2009;15(23):2652-64. doi: 10.2174/138161209788923949.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

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

Substances

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