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:: Volume 8, Issue 1 (Int J Mol Cell Med [In press] 2019) ::
Int J Mol Cell Med 2019, 8(1): 0-0 Back to browse issues page
The Epigenetic Regulation of Blinatumomab Gene Expression: Tumor Cell-dependent T cell Response against Lymphoma Cells and Cytotoxic Activity
Fatemeh Naddafi1, Fereidoun Mahboudi2, Maryam Tabarzad3, Zahra Aliabadi Farahani4, Farshad H. Shirazi1, Fatemeh Davami 5
1- Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2- Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
3- Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
5- Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. , f_davami@pasteur.ac.ir
Abstract:   (114 Views)
Conventional treatment for cancer such as surgical resection and chemotherapy can cause damage in cases with advanced cancers. Moreover, the identification of tumor-specific targets has great importance in T-cell therapies. For decades, T cell activity has been stimulated to improve anti-tumor activity. Bispecific antibodies have attracted strong interest from pharmaceutical companies, for their diagnostic and therapeutic use. Blinatumomab is a first-in-class bispecific T engager antibody for the treatment of relapsed or refractory precursor B- cell acute lymphoblastic leukemia. But, it can benefit several cases with CD19+ malignancies in the future. PhiC31 integrase-based vectors could selectively integrate therapeutic transgenes into pseudo-attP sites in CHO genome. In this study, production of Blinatumomab in CHO cells using this type of vectors was investigated. We evaluated the effects of histone deacetylases (HDACs) inhibitors such as sodium butyrate and valproic acid, on specific productivity and cell viability of antibody expressing cells. Although sodium butyrate increased specific productivity about 1.7-fold and valproic acid about 1.4-fold, valproic acid was found more efficient because of its less cytotoxic effect on cell growth. We examined the efficacy of expressed Blinatumomab at various effector to target (E/T) ratios. A dose-response analyses of calcein-acetoxymethyl release assay illustrated that the effective dose of expressed mAb required for antibody mediated cytotoxicity was 100 ng/ml and the expressed mAb was more effective at E/T ratios of 10:1 and 5:1. Results of this study indicated that the expressed blinatumomab can be useful for enhancing the cytotoxicity of CD3+ T-cells against CD19 + target cells in vitro.
Keywords: BiTE, T-cell activation, refractory acute lymphoid leukemia, therapeutic anti-CD19 mAb, Blinatumomab
     
Type of Study: Original Article | Subject: Genomics & Proteomics and Medical Biotechnology
Received: 2019/01/25 | Accepted: 2019/06/3
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Naddafi F, Mahboudi F, Tabarzad M, Aliabadi Farahani Z, H. Shirazi F, Davami F. The Epigenetic Regulation of Blinatumomab Gene Expression: Tumor Cell-dependent T cell Response against Lymphoma Cells and Cytotoxic Activity. Int J Mol Cell Med. 2019; 8 (1)
URL: http://ijmcmed.org/article-1-1015-en.html


Volume 8, Issue 1 (Int J Mol Cell Med [In press] 2019) Back to browse issues page
International Journal of Molecular and Cellular Medicine (IJMCM) International Journal of Molecular and Cellular Medicine (IJMCM)
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