{"id":"doi:10.1016/j.imlet.2019.02.004","kind":"article","title":"Identification of a neoantigen epitope in a melanoma patient with good response to anti-PD-1 antibody therapy","authors":["Chizu Nonomura","Masaki Otsuka","Ryota Kondou","Akira Iizuka","Haruo Miyata","Tadashi Ashizawa","Naoki Sakura","Shusuke Yoshikawa","Yoshio Kiyohara","Keiichi Ohshima","Kenichi Urakami","Takeshi Nagashima","Sumiko Ohnami","Masatoshi Kusuhara","Koichi Mitsuya","Nakamasa Hayashi","Yoko Nakasu","Tohru Mochizuki","Ken Yamaguchi","Yasuto Akiyama"],"author_count":20,"year":2019,"published":"2019-03-14","venue":"Immunology Letters","cited_by":14,"doi":"10.1016/j.imlet.2019.02.004","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.imlet.2019.02.004","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.imlet.2019.02.004","updated":null,"pmid":"30880120","pmcid":null,"openalex_id":"W2921060160","pdf_url":"https://www.sciencedirect.com/science/article/pii/S0165247818304887/pdf","abstract":"Recent advances in next-generation sequencing have enabled rapid and efficient evaluation of the mutational landscape of cancers. As a result, many cancer-specific neoantigens, which can generate antitumor cytotoxic T-cells inside tumors, have been identified. Previously, we reported a metastatic melanoma case with high tumor mutation burden, who obtained complete remission after anti-PD-1 therapy and surgical resection. The rib metastatic lesion, which was used for whole-exome sequencing and gene expression profiling in the HOPE project, showed upregulated expression of PD-L1 mRNA and a high single-nucleotide variants number of 2712. In the current study, we focused on a metastatic melanoma case and candidate epitopes among nonsynonymous mutant neoantigens of 1348 variants were investigated using a peptide-HLA binding algorithm, in vitro cytotoxic T-cell induction assay and HLA tetramer staining. Specifically, from mutant neoantigen data, a total of 21,066 9-mer mutant epitope candidates including a mutated amino acid anywhere in the sequence were applied to the NetMHC binding prediction algorithm. From in silico data, we identified the top 26 mutant epitopes with strong-binding capacity. A cytotoxic T-cell induction assay using 5 cancer patient-derived PBMCs revealed that the mutant ARMT1 peptide sequence (FYGKTILWF) with HLA-A*2402 restriction was an efficient neoantigen, which was detected at a frequency of approximately 0.04% in the HLA-A24 tetramer stain. The present success in identifying a novel mutant antigen epitope might be applied to clinical neoantigen screening in the context of an NGS-equipped medical facility for the development of the next-generation neoantigen cancer vaccines.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Identification of a neoantigen epitope in a melanoma patient with good response to anti-PD-1 antibody therapy\" by Chizu Nonomura, Masaki Otsuka, Ryota Kondou et al., https://doi.org/10.1016/j.imlet.2019.02.004, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"mrna-cancer-vaccines","name":"mRNA Therapeutics & Cancer Vaccines","domain_slug":"medicine"}],"cited_in_dossiers":[]}