Targeting FMS-related tyrosine kinase receptor 3 with the human immunoglobulin G1 monoclonal antibody IMC-EB10.

Abstract

FMS-related tyrosine kinase receptor 3 (FLT3) is a class III receptor tyrosine kinase that holds considerable promise as a therapeutic target in hematologic malignancies. Current efforts directed toward the development of small-molecule tyrosine kinase inhibitors of FLT3 may be limited by off-target toxicities and the development of drug resistance. Target-specific antibodies could overcome these hurdles and provide additional mechanisms to enhance the antitumor efficacy of FLT3 inhibitors. IMC-EB10 is a novel antibody directed against FLT3. The binding of IMC-EB10 to FLT3 results in antiproliferative effects in vitro and in mouse models engrafted with human leukemia cells that harbor wild-type or constitutively activated FLT3. Future clinical trials will test these notions formally and will identify the most appropriate opportunities for this member of a new generation of antileukemic therapies.

• Authors: Hagop Youssoufian, Eric K Rowinsky, James Tonra, Yiwen Li
• Journal: Cancer (Cancer) Vol. 116 Issue 4 Suppl Pg. 1013-7 (Feb 15 2010) ISSN: 0008-543X [Print] United States
• PMID: 20127944 (Publication Type: Journal Article)
• Copyright: (c) 2010 American Cancer Society.

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• IMC-EB10
• Immunoglobulin G
• Protein Kinase Inhibitors
• fms-Like Tyrosine Kinase 3

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Drug Delivery Systems
• Humans
• Immunoglobulin G (therapeutic use)
• Leukemia (drug therapy)
• Mice
• Mutation
• Protein Kinase Inhibitors (therapeutic use)
• fms-Like Tyrosine Kinase 3 (antagonists & inhibitors, genetics, immunology)