Keywords
Cetuximab; Erbitux; Biosimilar; Generic; Monoclonal; Mab; Antibody; EGFR; Cancer; Immunotherapy; Glycoform
Abstract
The monoclonal antibody (mAb) market has helped millions of patients across the globe in treating serious and chronic diseases. The expiry of patents for the first generation of approved therapeutic mAbs has led to the development and authorization of biosimilar alternatives for which the market is of great interest due to the demand of affordable treatments. Here we report the preclinical development of a biosimilar mAb to cetuximab (Erbitux®) referred to as CTL-1. Analyses of the physicochemical properties and biological activities of both CTL 1 and cetuximab were performed to allow for comparisons of the primary structure, glycoform heterogeneity, in vitro anti-tumor activity, and in vivo pharmacokinetics, tissue distribution, and efficacy of the two antibodies. Our results confirm that CTL-1 has the same amino acid sequence and a similar glycosylation profile as the cetuximab reference. In vitro bioassays indicate that CTL-1 and cetuximab achieve comparable dose-dependent inhibition of EGFR+ tumor cell proliferation, and maintain similar abilities to induce Antibody-Dependent Cell Mediated Cytotoxicity (ADCC). Preclinical studies in mice confirm that the proposed biosimilar to cetuximab is comparable with regard to its pharmacokinetic and tissue distribution properties as well as its ability to reduce tumor growth in vivo. Based on these comprehensive similarity studies, CTL-1 was confirmed to be highly similar to the reference mAb cetuximab and is suggested as a viable biosimilar alternative to this important therapeutic mAb.
Citation
Hu P, Graff R, Zheng L, Khawli LA and Epstein AL. Preclinical Characterization of CTL-1, A Biosimilar Anti-EGFR Monoclonal Antibody for Cetuximab. SM J Pharmac Ther. 2017; 3(2): 1017s.