A fibronectin scaffold approach to bispecific inhibitors of epidermal growth factor receptor and insulin-like growth factor-I receptor

Abstract

(2011) A fibronectin scaffold approach to bispecific inhibitors of epidermal growth factor receptor and insulin-like growth factor-I receptor , mAbs, 3:1, 38-48,

A stable IgG-like bispecific antibody targeting the epidermal growth factor receptor and the type I insulin-like growth factor receptor demonstrates superior anti-tumor activity

“…Here we report that a stability-engineered EGFR x IGF-1R bispecific antibody (EI-04) with IgG-like biophysical properties was capable of concurrently blocking the two growth factor receptor pathways and demonstrated superior anti-tumor activity in vitro and in vivo compared to single mAbs. Distinct from other reported EGFR x IGF-1R bispecific molecules, 37,41 this tetravalent bispecific antibody, perhaps due to increased binding avidity, also displayed greater activity than the combinations of single mAbs in several cases.…”

“…In this case, PEGylation was used to improve the solubility and serum half-life of this bispecific molecule, and the PEGylated bispecific Adnectin TM was shown to inhibit the growth of both EGFR and IGF-1R driven human tumor xenografts; however, it remains to be seen if this dual-targeting molecule is more efficacious compared to both EGFR and IGF-1R mAbs. 41 We previously reported a new and robust BsAb platform that utilizes stability-engineered scFvs appended to full length IgGs to target two tumor necrosis factor receptor family members or two distinct epitopes of IGF-1R. [42][43][44] Both BsAbs displayed IgGlike pharmaceutical properties, dual specificity and improved anti-tumor activity.…”

Development of a Carbon-14 Labeling Approach to Support Disposition Studies with a Pegylated Biologic

“…Huadong Sun, Brad Maxwell, Murli Krishna, and James Bryson (Bristol-Myers Squibb). We also thank Dr. Jochem Gokemeijer (Bristol-Myers Squibb) for providing the exposure data that were first reported by Emanuel et al (2011). …”

A Novel Glycoengineered Bispecific Antibody Format for Targeted Inhibition of Epidermal Growth Factor Receptor (EGFR) and Insulin-like Growth Factor Receptor Type I (IGF-1R) Demonstrating Unique Molecular Properties

“…In addition, a tetravalent bispecific antibody has been described devoid of ADCC effector functions, containing a C-terminal attachment of an IGF-1R scFv to the Fc part of an EGFR antibody (4). Another molecule lacking ADCC activity is a bispecific EGFR-IGF-1R inhibitor based on a human fibronectin scaffold, which has been PEGylated to increase serum half-life (30).…”