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Information Journal Paper

Title

The Epigenetic Regulation of Blinatumomab Gene Expression: Tumor Cell-dependent T cell Response against Lymphoma Cells and Cytotoxic Activity

Pages

  55-66

Abstract

 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.

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    APA: Copy

    NADDAFI, FATEMEH, MAHBOUDI, FEREIDOUN, TABARZAD, MARYAM, Aliabadi Farahani, Zahra, Hosein Shirazi, Farshad, & DAVAMI, FATEMEH. (2019). The Epigenetic Regulation of Blinatumomab Gene Expression: Tumor Cell-dependent T cell Response against Lymphoma Cells and Cytotoxic Activity. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE, 8(1), 55-66. SID. https://sid.ir/paper/332245/en

    Vancouver: Copy

    NADDAFI FATEMEH, MAHBOUDI FEREIDOUN, TABARZAD MARYAM, Aliabadi Farahani Zahra, Hosein Shirazi Farshad, DAVAMI FATEMEH. The Epigenetic Regulation of Blinatumomab Gene Expression: Tumor Cell-dependent T cell Response against Lymphoma Cells and Cytotoxic Activity. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE[Internet]. 2019;8(1):55-66. Available from: https://sid.ir/paper/332245/en

    IEEE: Copy

    FATEMEH NADDAFI, FEREIDOUN MAHBOUDI, MARYAM TABARZAD, Zahra Aliabadi Farahani, Farshad Hosein Shirazi, and FATEMEH DAVAMI, “The Epigenetic Regulation of Blinatumomab Gene Expression: Tumor Cell-dependent T cell Response against Lymphoma Cells and Cytotoxic Activity,” INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE, vol. 8, no. 1, pp. 55–66, 2019, [Online]. Available: https://sid.ir/paper/332245/en

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