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)

✍ Scribed by Jonathan D. Schwartz; Eric K. Rowinsky; Hagop Youssoufian; Bronislaw Pytowski; Yan Wu

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 223 KB
• Volume: 116
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/cncr.24789

✦ Synopsis

Abstract

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. Cancer 2010;116(4 suppl):1027–32. © 2010 American Cancer Society.