Abstract

Various strategies have been proposed for treatment of cancer, including common therapies such as surgery, chemotherapy, radiation therapy and advanced therapies such as monoclonal antibodies, antibody-drug conjugate (ADC), vaccines, chimeric antigen receptor T cells (CAR-T) and recombinant immunotoxins (RIT). One type of treatment that has recently been considered by many researchers is targeted therapy using immunotoxins. The 1F12-PE38KDEL is an immunotoxin that was designed in this paper against the EPHA2 receptor for the first time. EPHA2 is a member of the tyrosine kinase receptors family that is widely overexpressed in many cancer cells. The correct selection of the target receptor and the proper design of immunotoxin using bioinformatics methods are factors that determine the efficiency of the designed recombinant drug. Many features of the designed immunotoxin, including the second structure, tertiary structure, the ligand to receptor binding (docking), prediction of B cell epitopes and its correct folding have been examined by bioinformatics and experimental methods. Generally, our bioinformatics results showed that the mRNA expression and protein folding of immunotoxin is suitable; the functional domains of immunotoxin have been properly separated and the receptor-ligand binding has been performed in the correct point with appropriate orientations. Our experimental results including highly expression and proper folding of protein while some of bioinformatics prediction need more experimental studies. It is hoped that this immunotoxin due to having many of required specifications can play a pivotal role in treatment of some EPHA2-overexpressing cancers.