Vascular endothelial growth factor receptor-1 in human cancer: concise review and rationale for development of IMC-18F1 (Human antibody targeting vascular endothelial growth factor receptor-1).
The human vascular endothelial growth factor receptor-1 (VEGFR-1, or Flt-1) is widely expressed in normal and pathologic tissue and contributes to the pathogenesis of both neoplastic and inflammatory diseases. In human cancer, VEGFR-1 mediated signaling is responsible for both direct tumor activation and angiogenesis. VEGFR-1 mediated activation of nonmalignant supporting cells, particularly stromal, dendritic, hematopoietic cells, and macrophages, is also likely important for cancer pathogenesis. VEGFR-1 is also hypothesized to enable the development of cancer metastases by means of activation and premetastatic localization in distant organs of bone marrow-derived hematopoietic progenitor cells, which express VEGFR-1. IMC-18F1 is a fully human IgG(1) antibody that binds to VEGFR-1 and has been associated with the inhibition of cancer growth in multiple in vitro and human tumor xenograft models. The preliminary results of phase 1 investigations have also indicated a favorable safety profile for IMC-18F1 at doses that confer antibody concentrations that are associated with relevant antitumor activity in preclinical models.
Schwartz
Jonathan D
JD
ImClone Systems Corporation, 33 ImClone Drive, Branchburg, NJ 08876, USA. jonathan.schwartz@imclone.com
Rowinsky
Eric K
EK
Youssoufian
Hagop
H
Pytowski
Bronislaw
B
Wu
Yan
Y
D000818:Animals; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism; D018919:Neovascularization, Physiologic; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C548516:IMC-18F1; D008024:Ligands; D040281:Vascular Endothelial Growth Factor Receptor-1