In Silico Approach in Designing a Novel Multi-Epitope Vaccine Candidate against Non-Small Cell Lung Cancer with Overexpressed G Protein-Coupled Receptor 56.

Leana Rich M Herrera

doi:10.31557/apjcp.2020.21.8.2297

Abstract

Background:Majority of cancer-related deaths worldwide is attributed to non-small cell lung cancer (NSCLC). G protein-coupled receptor 56 (GPR56) is overexpressed and associated in the progression of NSCLC. The aim of this study is to use immunoinformatics approach in designing a multi-epitope vaccine to target overexpressed GPR56 which can potentially activate antibody-mediated cell death mechanisms and inhibit pathways involved in the proliferation, migration and survival of NSCLC. Methods:Herein, the reported overexpression of GPR56 was further investigated by conducting a differential gene expression analysis of NSCLC samples from GEO DataSets (GSE29249). Results confirmed significant overexpression of GPR56 in NSCLC compared to adjacent normal samples. A multi-epitope vaccine (Fvax) was constructed in silico by adjoining B lymphocytes (BL) and helper T lymphocytes (HTL) epitopes from the extracellular sequence of GPR56. Population coverage (PC) of HTL epitopes was also estimated. To enhance its immunogenicity, sequences of flagellin domains were fused as adjuvant. Fvax was evaluated in silico for antigenicity, allergenicity, peptide toxicity, physicochemical properties and cross-reactivity. Its tertiary structure was predicted, refined, and validated followed by structural epitope prediction. Lastly, Fvax DNA was optimized and cloned in silico. Results:This is the first work to design a potential vaccine against GPR56-overexpressing NSCLC. Fvax has 3 BL and 7 HTL immunogenic epitopes on GPR56. In silico evaluations suggest that Fvax is antigenic, non-toxic, non-allergenic, stable, and has accessible BL epitopes with high PC worldwide for HTL epitopes. Conclusion:Overall, results showed that Fvax is a potential vaccine against NSCLC. The approach of this study efficiently minimized the number of tests, cost and time required to select the best epitopes and to design a vaccine for the treatment of NSCLC.

Highlights

Lung cancer is the major cause of cancer-related deaths globally (Bray et al, 2018)
G protein-coupled receptors (GPRs) have been implicated in the development of diseases like cancer, one of these is the G Protein-Coupled Receptor 56 (GPR56) with 693 amino acid residues, encoded by Adhesion G-Protein Coupled Receptor G1 (ADGRG1) gene
Overexpression of G protein-coupled receptor 56 (GPR56) in non-small cell lung cancer (NSCLC) tissue samples Results showed that ADGRG1 is overexpressed approximately twice higher in NSCLC than the normal adjacent tissues

Summary

Introduction

Lung cancer is the major cause of cancer-related deaths globally (Bray et al, 2018). Approximately 87% of lung cancer cases are non-small cell lung cancer (NSCLC) (Grapatsas et al, 2017). Studies on cancer vaccines targeting tumor-associated antigens (TAA) have recently entered clinical trials with encouraging results (Kotsakis et al, 2014; Mizukoshi et al, 2015). Taking advantage of the overexpression and roles of GPR56 in NSCLC, designing a vaccine containing BL and HTL epitopes to induce immune responses against. The aim of this study is to use immunoinformatics approach in designing a multi-epitope vaccine to target overexpressed GPR56 which can potentially activate antibody-mediated cell death mechanisms and inhibit pathways involved in the proliferation, migration and survival of NSCLC. A multi-epitope vaccine (Fvax) was constructed in silico by adjoining B lymphocytes (BL) and helper T lymphocytes (HTL) epitopes from the extracellular sequence of GPR56. In silico evaluations suggest that Fvax is antigenic, non-toxic, non-allergenic, stable, and has accessible BL epitopes with high PC worldwide for HTL epitopes. The approach of this study efficiently minimized the number of tests, cost and time required to select the best epitopes and to design a vaccine for the treatment of NSCLC

Objectives

Methods

Results

Conclusion