Farideh Hosseinzadeh - Shiraz HIV/AIDS Research Center, Shiraz University of Medical Sciences, Shiraz, Iran-Recombinant antibody laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran
Saeed Mohammadi - Shiraz HIV/AIDS Research Center, Shiraz University of Medical Sciences, Shiraz, Iran-Recombinant antibody laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran
Foroogh Nejatollahi - Shiraz HIV/AIDS Research Center, Shiraz University of Medical Sciences, Shiraz, Iran-Recombinant antibody laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran

Background:  Cytotoxic T lymphocyte–associated antigen ۴ (CTLA-۴) molecules are expressed on T-cells and inhibit their function by inhibiting activation of subsequent T-cell molecular pathways. Blocking of CTLA-۴ inhibits the growth of malignant tumor cells. Anti-CTLA-۴ monoclonal antibodies activate the immune system against cancer. Due to several advantages of single-chain antibodies (scFvs) compared to monoclonal antibodies in cancer immunotherapy, specific anti-CTLA-۴ scFvs (single-chain variable fragment) were selected in this study. Methods: A phage antibody display library of scFvs was analyzed and a panning process was performed against an immunodominant epitope of CTLA-۴. PCR and DNA fingerprinting were used to differentiate the specific clones. The specificity of the selected clones was investigated by phage ELISA (Enzyme-linked immunosorbent assay). Results: Two specific clones with frequencies of ۳۵ and ۲۰% were identified. The clones reacted with the corresponding epitope on ELISA, while no reactivity was observed with an unrelated peptide, M۱۳KO۷ helper phage, unrelated scFvs, or no peptide as negative controls. Conclusions: Targeted therapy against cancer markers is an ideal treatment strategy. Specific human anti-CTLA-۴scFvs were selected in this study. These scFvs bound the related epitope. These antibodies have the potential to be used for targeted therapy, where the blocking of CTLA۴ receptor is needed. The study suggests further evaluation of the selected scFvs to reveal the effects of the selected antibodies.

Cancer immunotherapy, CTLA-۴, ScFv antibodies