1. Inhibitory Effect of Polyclonal Antibodies Against HER3 Extracellular Subdomains on Breast Cancer Cell Lines
- Author
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Mohammad Mehdi Amiri, Fazel Shokri, Mojgan Ghaedi, Samaneh Mansouri-Fard, Forough Golsaz-Shirazi, Jalal Khoshnoodi, Mohammad-Reza Shokri, Mahmood Jeddi-Tehrani, and Tannaz Bahadori
- Subjects
0301 basic medicine ,Receptor, ErbB-3 ,Antibodies, Neoplasm ,Receptor, ErbB-2 ,Immunization, Secondary ,Breast Neoplasms ,CHO Cells ,In Vitro Techniques ,Transfection ,Receptor tyrosine kinase ,law.invention ,Mice ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,Cricetulus ,Breast cancer ,0302 clinical medicine ,Protein Domains ,HER3 ,law ,Cell Line, Tumor ,fusion protein ,Extracellular ,Animals ,Humans ,skin and connective tissue diseases ,Receptor ,biology ,Chemistry ,Vaccination ,General Medicine ,polyclonal antibody ,Molecular biology ,Fusion protein ,In vitro ,030104 developmental biology ,Drug Resistance, Neoplasm ,Polyclonal antibodies ,Immunoglobulin G ,030220 oncology & carcinogenesis ,biology.protein ,Recombinant DNA ,Rabbits ,Dimerization ,Plasmids ,Research Article - Abstract
Objective Human epidermal growth factor receptor 3 (HER3) is a unique member of the tyrosine kinase receptors with an inactive kinase domain and is the preferable dimerization partner for HER2 which lead to potent tumorigenic signaling. Methods In this study, the expression plasmids coding for the human HER3 subdomains were transfected into CHO-K1 cells. Produced proteins were characterized by ELISA and SDS-PAGE. Rabbits were immunized and produced polyclonal antibodies (pAbs) that were characterized by ELISA, Immunoblotting and flowcytometry and their inhibitory effects were assessed by XTT on BT-474 and JIMT-1 breast cancer cell lines. Result The recombinant subdomains were highly immunogenic in rabbits. The pAbs reacted with the recombinant subdomains as well as commercial HER3 and the native receptor on tumor cell membranes and could significantly inhibit growth of Trastuzumab sensitive (BT-474) and resistant (JIMT-1) breast cancer cell lines in vitro. Conclusion It seems that HER3 extra cellular domains (ECD) induce a strong anti-tumor antibody response and may prove to be potentially useful for immunotherapeutic applications. .
- Published
- 2020