WT1 targeting multi-epitope vaccine design for glioblastoma multiforme using immuno-informatics approaches

Abstract

Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer classified as grade 4 glioma with a median survival rate of 12-14 months. Currently there is no cure and the conventional treatment outcomes are poor making it imperative to develop novel treatments. WT1, also known as Wilms Tumor 1, is a protein that is often found to be overexpressed in GBM and has minimal expression in normal tissues has become a promising target for immunotherapy for its oncogenicity and immunogenicity. This study aimed to develop a multi-epitope vaccine using immuno-informatics approaches that specifically targets the WT1 protein. The WT1 sequence was used to predict B and T cell epitopes which showed probable antigenic, non-allergic and non-toxic properties. Using suitable linker and adjuvants the vaccine construct (370 amino acids) was prepared which were then analyzed for solubility, physicochemical properties, molecular docking to show receptor interactions and molecular dynamics to show stability of the vaccine-receptor complexes. Subsequently, the vaccine sequence was back translated (1110 nucleotides), codon adaptation, pET-28a (+) vector in-silico cloning, and immune response simulations were performed. The designed vaccine lays groundwork for future in-vitro and in-vivo studies and potentially develop it into a novel treatment option for GBM patients.