{"id":"hum0327","version":1,"url":"https://humandbs.dbcls.jp/research/hum0327/v1","datePublished":"2022-02-25","versions":[{"version":1,"datePublished":"2022-02-25"}],"title":{"ja":"個別化T細胞受容体遺伝子導入T細胞療法の臨床応用を目指した肝胆膵領域がんにおけるネオアンチゲンおよびそれを認識するT細胞受容体のスクリーニング","en":"Screening of neoantigens and neoantigen reactive T cell receptors in hepatobiliary and pancreatic cancer for clinical application of personalized T cell therapy"},"summary":{"aims":{"ja":"肝胆膵領域のがんは患者数が多いだけでなく、根治することが難しいがんである。 近年、遺伝子変異により新しく生じた変異ペプチドが、ネオアンチゲンとして免疫系に認識されることが報告され、それらを標的とした免疫療法の開発が国内外で進められている。腫瘍内に浸潤しているT細胞の中には、このような遺伝子変異に由来するペプチドを認識し、活性化、浸潤した細胞分画が含まれていると考えられる。腫瘍内に浸潤しているT細胞が多様なネオアンチゲンを認識排除できるならば、それらを応用することで、がんの持つ不均一性に対応できるがん免疫治療法と成り得る可能性がある。本研究では、肝胆膵領域のがんに有効な免疫療法を開発し、がんの新しい治療法として提案するため、患者間で異なるがんの遺伝子変異や抗原を同定し、それらを認識する多様なT細胞集団を用いた免疫治療法の実用性の検証を行う。","en":"Cancers in the hepatobiliary and pancreatic regions are not only common but also difficult to cure. Recently, it has been reported that mutant peptides newly generated by genetic mutations are recognized by the immune system as neoantigens, and the development of immunotherapy targeting these peptides has been promoted. In this study, in order to develop effective immunotherapy for hepatobiliary and pancreatic cancers and to propose it as a new cancer therapy, we will first identify different genetic mutations and antigens in each patient with these cancers, and then verify the practicality of immunotherapy using a diverse population of T cells that recognize them."},"methods":{"ja":"外科的に切除された肝細胞がんおよび転移性肝がんから新鮮な正常組織と腫瘍組織を収集。それぞれの組織サンプル（直径2~5mm）からDNA/RNAを単離し、NextSeq 550（イルミナ）による全エキソームシーケンスまたはRNAシーケンスに用いた。","en":"Paired fresh normal and tumor tissues were collected from surgically resected HCC and mCRC. RNA and genomic DNA were extracted from tumor/normal tissues (2-5 mm in diameter) and used for whole exome sequencing or RNA sequencing with NextSeq 550 (Illumina)."},"targets":{"ja":"2017年から2020年において、国立がん研究センター東病院で外科的切除術を受けた肝がん症例","en":"Tumor tissues were collected from liver cancer patients, who were received surgical resection at the National Cancer Center Hospital East (NCCE) between 2017 and 2020."},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"配列決定\n発現","en":"Sequencing, Expression profiling"},"targets":{"ja":"肝細胞癌：28症例\n転移性肝癌：18症例\n（日本人）","en":"hepatocellular carcinoma: 28 cases\nmetastatic colorectal carcinoma: 18 cases\n(Japanese)"},"typeOfData":{"ja":"NGS\n（Exome、RNA-seq）","en":"NGS\n(Exome, RNA-seq)"}},"releaseNote":{"ja":"肝細胞がんおよび転移性肝がんの腫瘍組織および非腫瘍組織から抽出したDNA/RNAを用いたwhole exome sequencingならびにRNA-seq解析データをfastq、vcf、tpmファイル形式で提供する。","en":"DNAs/RNAs extracted from tumor and paired non-tumor tissues of hepatocellular carcinoma or metastatic colorectal carcinoma patients were used for the whole exome sequencing and RNA sequencing analyses. Fastq, vcf, and tpm files are provided."},"dataProviders":[{"name":{"ja":"鈴木 利宙","en":"Toshihiro Suzuki"},"organization":{"name":{"ja":"国立がん研究センター 先端医療開発センター 免疫療法開発分野","en":"Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center"}}}],"researchProjects":[{"name":{"ja":"がん個別化がんワクチン療法の開発","en":"Development of personalize neoantigen vaccine"},"url":{"ja":[{"url":"https://www.ncc.go.jp/jp/epoc/division/immunotherapy/kashiwa/030/020/20170728190117.html","text":"https://www.ncc.go.jp/jp/epoc/division/immunotherapy/kashiwa/030/020/20170728190117.html"}],"en":[{"url":"https://www.ncc.go.jp/en/epoc/division/immunotherapy/kashiwa/030/020/20170728190117.html","text":"https://www.ncc.go.jp/en/epoc/division/immunotherapy/kashiwa/030/020/20170728190117.html"}]}}],"grants":[{"title":{"ja":"完全個別化ネオアンチゲンワクチン療法の手法の開発","en":"Development of the methodology for individualized neoantigen vaccine therapy"},"agency":{"ja":"ブライトパス・バイオ株式会社との共同研究費","en":"Collaboration funding from BrightPath Biotherapeutics Co., Ltd."},"grantIds":["C2017-054"]}],"relatedPublications":[{"title":"Development of antigen-prediction algorithm for personalized neoantigen vaccine using human leukocyte antigen transgenic mouse","doi":"https://doi.org/10.1111/cas.15291","datasets":["JGAD000624"]}],"datasets":["JGAD000624"],"controlledAccessUsers":[{"principalInvestigator":{"ja":"浜田 道昭","en":"Michiaki Hamada"},"affiliation":{"ja":"浜田研究室, 理工学術院, 早稲田大学","en":"Hamada Laboratory, Faculty of Science and Engineering, Waseda University"},"country":{"ja":"日本","en":"Japan"},"researchTitle":{"ja":"RNA標的創薬データベースの構築","en":"Construction of RNA-targeted Drug Discovery Database"},"periodStart":"2023-01-05","periodEnd":"2027-10-31","datasets":["JGAD000624"]}]}