Engineering a variant of IL-17RA with high binding affinity to IL-17A for optimized immunotherapy

ABSTRACT: Highlights • Engineered IL-17RA can bind to IL-17A with high binding affinity.• Engineered IL-17RA can block IL-17A and IL-17RA interaction.• Engineered IL-17RA can be used in immunotherapy. Immunotherapy is one of the most recently used treatments for numerous cancer types and also some autoimmune and inflammatory diseases. One of the valuable targets for immunotherapy is Interleukin-17A (IL-17A) or its receptor (IL-17RA) because overexpression of IL-17A as a pro-inflammatory cytokine is associated with several inflammatory, autoimmune and cancer diseases. In this study, the extracellular domain of IL-17RA involved in binding to IL-17A was mutated by using R software to achieve a variant with increased binding affinity to IL-17A. The ∆∆G value of –30.89 kcal/mol was calculated for the best variant (385) with point mutations of R265N, N91T, and W31K using the FoldX module. Also, the KD for its interaction with IL-17A was calculated 0.06 nM by surface plasmon resonance (SPR) technique. Our results indicated that variant 385 could bind to IL-17A with higher binding affinity than wild-type one, so, it can be a good therapeutic candidate for blocking IL-17A.

SUBMITTER: Armaghan F 

PROVIDER: S-EPMC8572878 | biostudies-literature |

REPOSITORIES: biostudies-literature