Development of cancer vaccine therapy targeting individual genetic mutations identified by next generation sequencing

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659625
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Thoracic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: NAKAJIMA Jun 東京大学, 医学部附属病院, 教授 (90188954)
• Co-Investigator(Kenkyū-buntansha): MURAKAWA Tomohiro 東京大学, 医学部附属病院, 講師 (50359626) ; SANO Atsushi 東京大学, 医学部附属病院, 登録研究員 (20569834) ; KAKIMI Kazuhiro 東京大学, 医学部附属病院, 特任教授 (80273358) ; MATSUSHITA Hirokazu 東京大学, 医学部附属病院, 特任講師 (80597782)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肺がん / 次世代シーケンス / 遺伝子変異 / MHCクラスＩ結合予測法 / 固有抗原 / 変異ペプチド / 免疫反応 / 個別化がん免疫治療

Outline of Final Research Achievements

We established the method to identify candidate unique antigens from cancer specific mutations in pancreatic cancer specimens by combining next generation sequencing with MHC class I binding algorism. We also developed an assay to verify immune responses against those candidate unique antigens in mice. In total 6 lung cancer patients consisting of 3 smokers and 3 non-smokers, the numbers of genetic mutations (missense mutations) were 280 on average in former versus 75 in latter. Accordingly, the numbers of candidate unique antigen-derived T cell epitopes predicted by the algorism were 535 on average in former versus 140 in latter. We successfully created the system predicting candidate unique antigens and verifying them, which is a prerequisite for individualized cancer immunotherapy development in lung cancer patients.

Free Research Field

呼吸器外科学