Screening Of EGFR Mutational Peptide As Cancer Vaccine For Lung Cancer

Background: Neoantigen is a kind of tumor specific antigen which is not expressed in normal tissues but only exists in tumor cells and stimulates the immune response to produce specific T cell.Because normal tissues do not possess these antigens,neoantigen-specific T cells are not subject to central and peripheral tolerance,and also lack the ability to induce normal tissue destruction.The data to date indicate that the vast majority of mutated antigens are not shared between patients,and are considered patient-specific.So far,the neoantigen peptide vaccine has been reported,which is customized according to the patient’s personalized vaccine.This limits the large-scale development of tumor vaccines based on neoantigen.85% of the patients with lung cancer are non-small cell lung cancer(NSCLC).The mutation rate of human epidermal growth factor receptor(EGFR)gene in non-small cell lung cancer(NSCLC)is over 60%.The mutation loci are mostly concentrated in the 18-21 exon region.After taking tyrosine kinase inhibitor drugs,more than 90% of patients who tolerated drugs were due to the 19 exon T790 M mutation.High mutation rate of EGFR gene in patients with lung cancer,neoantigen screened for mutant peptides produced by EGFR mutations may be universal in the treatment of patients with lung cancer.Objective: Screening EGFR mutant short peptides that can induce specific cellular immunity,and provide potential neoantigen for lung cancer vaccine research and development.Methods:1.Forty mutant peptides with lengths of ten amino acids were synthesized on the basis of common mutations in the 18-21 exon region of EGFR gene.2.Co-cultured with peripheral blood lymphocytes(PBMC)of lung cancer patients to identify EGFR mutant peptides that could induce the T cell activation,and measured by cytokine(IFN-γ)secretion or the growth of cell.3.Admixed with the screened EGFR mutant peptides and complete Freund’s adjuvant(CFA),we evaluated effective mutant peptide via in vivo experiment of mice and verify the effect of the mutant short peptide.Results:1.Three short peptides were screened through in vitro experiments.The short peptide was mixed with complete Freund’s adjuvant to make the antigen emulsion.Induce immunization in mice.2.Three kinds of short peptides have the effect of stimulating immunity in vivo.The effect of 16# than the other two kinds of peptide effects.