Rationale for the development of IMC-3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet-derived growth factor receptor α

Gaurav D. Shah, Nick Loizos, Hagop Youssoufian, Jonathan D. Schwartz, Eric K. Rowinsky

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

A large body of evidence suggests that the platelet-derived growth factor (PDGF) family and associated receptors are potential targets in oncology therapeutic development because of their critical roles in the proliferation and survival of various cancers and in the regulation and growth of the tumor stroma and blood vessels. Several small molecules that nonspecifically target the PDGF signaling axis are in current use or development as anticancer therapies. However, for the majority of these agents, PDGF and its receptors are neither the primary targets nor the principal mediators of anticancer activity. IMC-3G3, a fully human monoclonal antibody of the immunoglobulin G subclass 1, specifically binds to the human PDGF receptor α (PDGFRα) with high affinity and blocks PDGF ligand binding and PDGFRα activation. The results of preclinical studies and the frequent expression of PDGFRα in many types of cancer and in cancer-associated stroma support a rationale for the clinical development of IMC-3G3. Currently, IMC-3G3 is being evaluated in early clinical development for patients with several types of solid malignancies.

Original languageEnglish
Pages (from-to)1018-1026
Number of pages9
JournalCancer
Volume116
Issue numberSUPPL. 4
DOIs
StatePublished - 15 Feb 2010
Externally publishedYes

Keywords

  • Antineoplastic agents
  • Cancer-associated stroma
  • Malignant stroma
  • Monoclonal antibodies
  • Neoplasms
  • Platelet-derived growth factor
  • Platelet-derived growth factor receptor α
  • Tumor-associated stroma
  • Vascular endothelial growth factors

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