Screening and immune activity detection of neoantigen vaccine targeting epidermal growth factor receptor mutation of non-small cell lung cancer / 中国肿瘤临床

ABSTRACT

Objective: This study aims to screen the optional epitope peptides of HLA-A*02 restricted human epidermal growth factor receptor (EGFR) exon20 insertion mutations in order to provide a novel immunotherapeutic strategy for non-small cell lung cancer (NSCLC). Methods: HLA-A*02 restricted epitopes derived from EGFR exon20 insertion mutation were predicted by IEDB, NetMHC4.0 and SYFPEITHI. The cytotoxic T lymphocyte (CTL) epitope-concentrated area was analyzed, and the appropriate length of polypeptides were filtered. Both cell experiments and mice models were implemented to verify the immunogenicity and antitumor efficiency of the candidate polypeptides. Results: V769_D770insASV (19.35%) mutation is a high-frequency EGFR exon20 insertion in NSCLC, which encoded YVMASVASV polypeptide with higher MHC class I binding score than other insertions. E-ASV-10 and E-ASV-19, both possessing the core sequence of YVMASVASV polypeptide, were capable to induce the expansion and activation of HLA-A*02 restricted T cells in vitro, displaying increase in the proportion of 4-1BB+CD25+ population and the production and release of IFN-γ in CD4+ and CD8+ T cells. E-ASV-10 stimulated the amplification of cytotoxic T cells against the LLC cells carrying th eEGFR exon20 V769_D770insASVmutation(LLCasv) in C57BL/6 mice. Conclusions: E-ASV-10 and E-ASV-19 could induce the expansion and activation of human HLA-A* 02 restricted T cells in vitro, and stimulate specific cytotoxic CTL response against LLCasv in C57BL/6 mice, which might become an promosing immunotherapeutic approach for NSCLC patients carrying EGFR exon20 V769_D770insASV mutation.