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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی:
- چکیده:
- چکیده انگلیسی:
- انتشار مقاله: 23-12-1397
- نویسندگان: Mohammad Mehdi Amiri,Tannaz Bahadori,Tahereh Soltantoyeh,Reza Hosseini-Ghatar,Forough Golsaz-Shirazi,Mahmood Jeddi-Tehrani,Fazel Shokri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Immunology
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,HER2,Immunotherapy,Polyclonal antibody,subdomains of HER2
- چکیده:
- چکیده انگلیسی: Background: Human epidermal growth factor receptor 2 (HER2) has a crucial role in several malignancies. The extracellular domain of HER2 (HER2-ECD) has been extensively employed as an important target in passive and active immunotherapy. Isolated recombinant prokaryotic HER2-ECD subdomains were previously found to be ineffective in inducing anti-tumor antibody response. Objective: To employ recombinant eukaryotic HER2-ECD subdomains to raise anti-HER2 antibodies and determine their anti-tumor activity in vitro. Methods: Two paired subdomains of HER2-ECD (DI+II and DIII+IV), representing Pertuzumab and Trastuzumab binding domains, respectively, along with the full extracellular domain of HER2 were generated in CHO-K1 cells. Polyclonal antibodies were raised against these subdomains and characterized using ELISA, flow cytometry, and immunoblot and their anti-tumor activity was assessed by XTT assay. The cross-reactivity of these antibodies was specified along with other members of the human HER family. Results: Similar to Trastuzumab and anti-HER2-ECD antibody, anti-DI+II and DIII+IV polyclonal antibodies reacted with recombinant HER2-ECD and native HER2 expressed on tumor cells. These two polyclonal antibodies were able to inhibit the binding of Pertuzumab and Trastuzumab to HER2, respectively, and did not cross-react with other members of HER family. These antibodies were able to inhibit tumor cell growth in vitro, similar to Trastuzumab. Conclusion: The high immunogenicity of human HER2 DI+II and DIII+IV subdomains in rabbits and the tumor inhibitory activity of the purified specific antibodies imply that they might be suitable for active immunotherapy in formulation with appropriate adjuvants and in combination with other HER2 specific therapeutics.
- انتشار مقاله: 27-06-1396
- نویسندگان: Reza Hosseini-Ghatar,Tahereh Soltantoyeh,Motahareh Bahadori,Jalal Khoshnoodi,Forough Golsaz-Shirazi,Mahmood Jeddi-Tehrani,Mohammad Mehdi Amiri,Fazel Shokri
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Fusion protein,HER3,Polyclonal antibody
- چکیده:
- چکیده انگلیسی: 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.
- انتشار مقاله: 21-05-1398
- نویسندگان: Samaneh Mansouri-Fard,Mojgan Ghaedi,Mohammad-Reza Shokri,Tannaz Bahadori,Jalal Khoshnoodi,Forough Golsaz-Shirazi,Mahmood Jeddi-Tehrani,Mohammad Mehdi Amiri,Fazel Shokri
- مشاهده