Isolation and characterization of anti ROR1 single chain fragment variable antibodies using phage display technique

Article type: Research Article

Authors: Aghebati-Maleki, Leili^{a; b; c} | Younesi, Vahid^{d; e} | Jadidi-Niaragh, Farhad^{b; f} | Baradaran, Behzad^{a; f} | Majidi, Jafar^{a; f; *} | Yousefi, Mehdi^{b; f; *}

Affiliations: [a] Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran | [b] Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran | [c] Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran | [d] Faculty of Paramedical Sciences, Alborz University of Medical Sciences, Karaj, Iran | [e] Pishtaz Teb Zaman Diagnostics, Tehran, Iran | [f] Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Correspondence: [*] Corresponding authors: Mehdi Yousefi, Jafar Majidi, Department of Immunology. Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Tel.: +984133364665; E-mail:yousefime@tbzmed.ac.ir;jmajidiz@yahoo.com

Abstract: Receptor tyrosine kinase-like orphan receptor (ROR1) belongs to one of the families of receptor tyrosine kinases (RTKs). RTKs are involved in the various physiologic cellular functions including proliferation, migration, survival, signaling and differentiation. Several RTKs are deregulated in various cancers implying the targeting potential of these molecules in cancer therapy. ROR1 has recently been shown to be expressed in various types of cancer cells but not in normal adult cells. Hence a molecular inhibitor of extracellular domain of ROR1 that inhibits ROR1-cell surface interaction is of great therapeutic importance. In an attempt to develop molecular inhibitors of ROR1, we screened single chain variable fragment (scFv) phage display libraries, Tomlinson I + J, against one specific synthetic oligopeptide from extracellular domain of ROR1 and selected scFvs were characterized using various immunological techniques. Several ROR1 specific scFvs were selected following five rounds of panning procedure. The scFvs showed specific binding to ROR1 using immunological techniques. Our results demonstrate successful isolation and characterization of specific ROR1 scFvs that may have great therapeutic potential in cancer immunotherapy.

Keywords: ROR1, scFv, phage display technique, receptor tyrosine kinases

DOI: 10.3233/HAB-170310

Journal: Human Antibodies, vol. 25, no. 1-2, pp. 57-63, 2017