Inhibitory Effect of Polyclonal Antibodies Against HER3 Extracellular Subdomains on Breast Cancer Cell Lines.

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.<br />.

• Authors: Samaneh Mansouri-Fard, Mojgan Ghaedi, Mohammad-Reza Shokri, Tannaz Bahadori, Jalal Khoshnoodi, Forough Golsaz-Shirazi, Mahmood Jeddi-Tehrani, Mohammad Mehdi Amiri, Fazel Shokri
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 21 Issue 2 Pg. 439-447 (Feb 01 2020) ISSN: 2476-762X [Electronic] Thailand
• PMID: 32102522 (Publication Type: Journal Article)

Chemical References

• Antibodies, Neoplasm
• Antineoplastic Agents, Immunological
• Immunoglobulin G
• ERBB2 protein, human
• ERBB3 protein, human
• Receptor, ErbB-2
• Receptor, ErbB-3

Topics

• Animals
• Antibodies, Neoplasm (immunology, pharmacology)
• Antineoplastic Agents, Immunological (pharmacology)
• Breast Neoplasms (drug therapy, immunology, metabolism)
• CHO Cells
• Cell Line, Tumor
• Cricetulus
• Dimerization
• Drug Resistance, Neoplasm
• Humans
• Immunization, Secondary
• Immunoglobulin G
• In Vitro Techniques
• Mice
• Plasmids
• Protein Domains (immunology)
• Rabbits
• Receptor, ErbB-2 (metabolism)
• Receptor, ErbB-3 (immunology)
• Transfection
• Vaccination