Production and Characterization of New Anti-HER2 Monoclonal Antibodies

Abstract

Breast cancer is a major public health problem worldwide. Although in Iran cancer is the third cause of death after coronary heart disease and accidents, mortality from cancer has been on the rise during recent decades. About 15% to 20% of patients with invasive breast cancer have abnormally high levels of HER2 protein. HER2 is a specialized protein found on breast cancer cells that controls cancer growth and spread. This study describes the generation and characterization of new anti-HER2 MAbs towards HER2 protein using a chimeric peptide immunogen containing discontinuous B-cell epitope peptide (peptide 626) and promiscuous T-helper epitope (MVF). The specificity of these MAbs was confirmed in various immunoassays, including ELISA, Western blotting, and immunofluorescence. Moreover, the MTT assay results indicated that 5H5 and 5H11 MAbs could reduce the growth of SKBR3 cells by approximately 50% (p<0.05). These MAbs that can reduce cancer cell proliferation would be useful for cancer therapy. Furthermore, the synthetic peptide used in the current work was able to induce the immune system to generate antibodies, especially IgG isotype. Therefore, it could be further used as a peptide cancer vaccine that targets different epitopes or structural domains of HER2 ECD.

Conformational characterization of a novel anti-HER2 candidate antibody

“…Trastuzumab (Herceptin, Roche) is a humanized mAb directed toward the epidermal growth factor receptor type 2 (HER2 or HER-2/neu), which is overexpressed in 15 to 30% of invasive breast adenocarcinomas [5]. It was the first mAb approved in 1998 by the Food and Drug Administration of the United States of America (FDA) and also by the European Medicines Agency (EMA) in 2000 for the treatment of breast cancer patients with advanced or metastatic disease [6, 7]. Therapeutic schemes using Herceptin significantly provide clinical benefits in treated patients [6, 7].…”

“…It was the first mAb approved in 1998 by the Food and Drug Administration of the United States of America (FDA) and also by the European Medicines Agency (EMA) in 2000 for the treatment of breast cancer patients with advanced or metastatic disease [6, 7]. Therapeutic schemes using Herceptin significantly provide clinical benefits in treated patients [6, 7].…”