Design and Evaluation of Scfv-Rtx-A As a Novel Immunotoxin for Breast Cancer Treatment: An in Silico Approach Publisher Pubmed



Samavarchi Tehrani S^{1, 2} ; Gharibi S³ ; Movahedpour A^{3, 4} ; Goodarzi G^{1, 2, 5} ; Jamali Z⁶ ; Khatami SH⁷ ; Maniati M⁸ ; Ranjbar M³ ; Shabaninejad Z^{9, 10} ; Savardashtaki A^{3, 10} ; Taherianganeh M¹¹
Source: Journal of Immunoassay and Immunochemistry Published:2021

Abstract

Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast cancer (BC) patients. Hence, immunotherapy is a proper treatment option for HER2-positive BC patients. Accumulating evidence has indicated that immunotoxin therapy is a novel approach to improve the potency of targeted therapy. Immunotoxins are antibodies or antibody fragments coupled with a toxin. We designed an immunotoxin. The physicochemical properties were evaluated using ProtParam servers and secondary structure was examined by PROSO II and GORV. Using I-TASSER, a 3D model was built and refined by GalaxyRefine. The model was validated using PROCHECK and RAMPAGE. To predict immunotoxin allergenicity and mRNA stability, AlgPred server and RNAfold were used. Furthermore, the immunotoxin and HER2 were docked by ZDOCK. The scFv+RTX-A could be a non-allergenic and stable chimeric protein, and the secondary structure of its components did not alter, and this protein had a proper 3D structure that might have stable mRNA structure which could bind to HER2. Given the fact that the designed immunotoxin was a non-allergenic and stable chimeric protein and that it could bind with high affinity to HER2 receptors, we proposed that this chimeric protein could be a useful candidate for HER-2 positive BC patients. © 2020 Taylor & Francis.