Targeting FMS-related tyrosine kinase receptor 3 with the human immunoglobulin G1 monoclonal antibody IMC-EB10.
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.
Youssoufian
Hagop
H
ImClone Systems Corporation, 33 ImClone Drive, Branchburg, NJ 08876, USA. hagop.youssoufian@imclone.com
Rowinsky
Eric K
EK
Tonra
James
J
Li
Yiwen
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007938:Leukemia / Q000188:drug therapy*; D051379:Mice; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C548514:IMC-EB10; D007074:Immunoglobulin G; D047428:Protein Kinase Inhibitors; D051941:fms-Like Tyrosine Kinase 3