Repository of Research and Investigative Information

Repository of Research and Investigative Information

Baqiyatallah University of Medical Sciences

Preparation and In Vitro Evaluation of Antitumor Activity of TGF alpha L3-SEB as a Ligand-Targeted Superantigen

(2016) Preparation and In Vitro Evaluation of Antitumor Activity of TGF alpha L3-SEB as a Ligand-Targeted Superantigen. Technology in Cancer Research & Treatment. pp. 215-226. ISSN 1533-0346

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Abstract

Tumor-targeted superantigens (TTSs) have been used to treat a variety of tumors in preclinical studies. The TTS utilizes the powerful T-cell activation strategy by means of staphylococcal enterotoxins (SEs) as superantigens (Sags) to target tumor cells. Monoclonal antibodies and tumor-related ligands have been used as targeting molecules of Sag. In this study, we assessed the antitumor potency of tumor-targeted superantigen (TTS) strategy to design and produce fusion protein as a new antitumor candidate. The third loop (L3) of transforming growth factor alpha (TGF-alpha) was genetically conjugated to staphylococcal enterotoxin type B (TGF alpha L3-SEB), and its in vitro antitumor activity against murine breast cancer cells (A431 cell line) was evaluated. We designed and prepared TGF alpha L3-SEB chimeric protein and evaluated superantigenic activity, binding property to cancer cells, overexpression of epidermal growth factor receptor (EGFR), and in vitro antitumor activities. Cloning of tgfl3-seb was confirmed by colony-polymerase chain reaction, enzymatic digestion, and sequencing. The recombinant TGF alpha L3-SEB fusion protein with molecular weight of 31 kDa was expressed and confirmed by anti-His Western-blot analysis. The TGF alpha L3-SEB fusion protein attached to A431 cell line with proper affinity and induced dose-dependent cytotoxicity against EGFR-expressing cancer cells in vitro. The TGF alpha L3-SEB chimeric protein exhibited potent in vitro antitumor activity. Our findings indicated that TGF alpha L3-SEB may be a promising anticancer candidate in cancer immunotherapy, and further studies are required to explore its potential in vivo therapeutic applications.

Item Type: Article
Keywords: breast cancer cloning and expression immunotherapy staphylococcal enterotoxin type B (SEB) transforming growth factor alpha (TGF-alpha) epidermal-growth-factor staphylococcal-enterotoxin-b breast-cancer metastasis mouse mammary-tumor factor receptor class-ii t-cells therapy stimulation model Oncology
Divisions:
Page Range: pp. 215-226
Journal or Publication Title: Technology in Cancer Research & Treatment
Journal Index: ISI
Volume: 15
Number: 2
Identification Number: https://doi.org/10.1177/1533034614568753
ISSN: 1533-0346
Depositing User: مهندس مهدی شریفی
URI: http://eprints.bmsu.ac.ir/id/eprint/5070

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