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Updated: Jun 16, 2026
A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity
Published on: July 12, 2018
Rationale for the development of IMC-3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the
Gaurav D Shah1, Nick Loizos, Hagop Youssoufian
1ImClone Systems Corporation, 33 ImClone Drive, Branchburg, NJ 08876, USA. gaurav.shah@imclone.com
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 alpha (PDGFRalpha) with high affinity and blocks PDGF ligand binding and PDGFRalpha activation. The results of preclinical studies and the frequent expression of PDGFRalpha 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.
Insights
Platelet-derived growth factor receptor alpha (PDGFRalpha) is crucial in cancer growth. IMC-3G3, a novel antibody, targets PDGFRalpha, showing promise for solid tumor therapies.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Platelet-derived growth factor (PDGF) signaling is implicated in cancer proliferation, survival, and tumor microenvironment regulation.
- Existing therapies targeting the PDGF axis lack specificity, with PDGF receptors not being the primary targets.
- Frequent expression of PDGF receptor alpha (PDGFRalpha) in various cancers suggests its therapeutic potential.
Purpose of the Study:
- To evaluate IMC-3G3, a monoclonal antibody targeting PDGFRalpha, as a potential anticancer therapeutic.
- To investigate the specific binding and inhibitory effects of IMC-3G3 on PDGFRalpha activation.
Main Methods:
- Development of a fully human monoclonal antibody (IMC-3G3) targeting PDGFRalpha.
- Preclinical studies assessing IMC-3G3's binding affinity and inhibitory function.
- Evaluation of PDGFRalpha expression in diverse cancer types and associated stroma.
Main Results:
- IMC-3G3 demonstrates high-affinity specific binding to human PDGFRalpha.
- The antibody effectively blocks PDGF ligand binding and PDGFRalpha activation.
- Preclinical data and PDGFRalpha expression patterns support its clinical rationale.
Conclusions:
- IMC-3G3 represents a targeted therapeutic strategy against PDGFRalpha-expressing cancers.
- The antibody's specific mechanism offers a potential advantage over non-specific agents.
- IMC-3G3 is currently undergoing early clinical evaluation for solid malignancies.
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