Comprehensive analysis of immune responses to tumor-specific genetic mutations and its application to novel cancer immunotherapy.

• Project/Area Number: 26293293
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kanagawa Cancer Center Research Institute
• Principal Investigator: Sasada Tetsuro 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), がんワクチンセンター, 部長 (70293967)
• Co-Investigator(Kenkyū-buntansha): 田代 康介 九州大学, (連合)農学研究科(研究院), 准教授 (00192170)
• Co-Investigator(Renkei-kenkyūsha): MATSUEDA Satoko 久留米大学, 先端がん治療研究センター, 講師 (60610582)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 腫瘍免疫 / 遺伝子変異 / 免疫反応 / がん免疫療法 / ネオアンチゲン / 免疫原性 / Ｔ細胞 / 個別化治療 / 免疫療法

Outline of Final Research Achievements

We comprehensively investigated immune responses to tumor-specific gene mutations identified in individual cancer patients. The detailed immunological analyses have demonstrated that neoantigens derived from tumor-specific mutations (especially passenger mutations) show high immunogenicity and induce antigen-specific T cell responses efficiently. Our findings suggest that neoantigens might play critical roles in anti-tumor immunity, and could provide important information for further development of “personalized cancer immunotherapy targeting mutation-derived neoantigens” as a novel cancer treatment modality.

Research Products

• [Journal Article] Feasibility Study of Personalized Peptide Vaccination for Advanced Small Cell Lung Cancer. (2017)
  • Author(s): Sakamoto S, Yamada T, Terazaki Y, Yoshiyama K, Sugawara S, Takamori S, Matsueda S, Shichijo S, Yamada A, Noguchi M, Itoh K, Hattori N, Kohno N, Sasada T.
  • Journal Title: Clin Lung Cancer. Volume: 印刷中 Issue: 6 Pages: e385-e394
  • DOI: 10.1016/j.cllc.2017.03.011
  • Peer Reviewed / Open Access
• [Journal Article] Enhancement of humoral and cell mediated immune response to HPV16 L1-derived peptides subsequent to vaccination with prophylactic bivalent HPV L1 virus-like particle vaccine in healthy females. (2017)
  • Author(s): Yokomine M, Matsueda S, Kawano K, Sasada T, Fukui A, Yamashita T, Komatsu N, Shichijo S, Tasaki K, Matsukuma K, Itoh K, Kamura T, Ushijima K.
  • Journal Title: Exp Ther Med. Volume: 13 Issue: 4 Pages: 1500-1505
  • DOI: 10.3892/etm.2017.4150
  • Peer Reviewed / Open Access
• [Journal Article] A randomized phase II trial of personalized peptide vaccine with low dose cyclophosphamide in biliary tract cancer. (2017)
  • Author(s): Shirahama T, Muroya D, Matsueda S, Yamada A, Shichijo S, Naito M, Yamashita T, Sakamoto S, Okuda K, Itoh K, Sasada T, Yutani S.
  • Journal Title: Cancer Sci. Volume: 印刷中 Issue: 5 Pages: 838-845
  • DOI: 10.1111/cas.13193
  • Peer Reviewed / Open Access
• [Journal Article] Immunological evaluation of peptide vaccination for cancer patients with the HLA -A11+ or -A33+ allele. (2017)
  • Author(s): Sakamoto S, Matsueda S, Takamori S, Toh U, Noguchi M, Yutani S, Yamada A, Shichijo S, Yamada T, Suekane S, Kawano K, Naitou M, Sasada T, Hattori N, Kohno N, Itoh K.
  • Journal Title: Cancer Sci. Volume: 印刷中 Issue: 4 Pages: 598-603
  • DOI: 10.1111/cas.13189
  • Peer Reviewed / Open Access
• [Journal Article] 遺伝子変異新規抗原（ネオアンチゲン）を標的としたがん免疫療法 (2017)
  • Author(s): 笹田哲朗
  • Journal Title: 日本臨床 （特集）がん免疫療法 Volume: 75 (2) Pages: 189-195
• [Journal Article] Current status and future prospects of peptide-based cancer vaccines. (2016)
  • Author(s): Wada S, Yada E, Ohtake J, Fujimoto Y, Uchiyama H, Yoshida S, Sasada T.
  • Journal Title: Immunotherapy. Volume: 8 Issue: 11 Pages: 1321-1333
  • DOI: 10.2217/imt-2016-0063
  • Peer Reviewed
• [Journal Article] Immune Responses to Epidermal Growth Factor Receptor (EGFR) and Their Application for Cancer Treatment. (2016)
  • Author(s): Sasada T, Azuma K, Ohtake J, Fujimoto Y.
  • Journal Title: Front Pharmacol. Volume: 7 Pages: 405-405
  • DOI: 10.3389/fphar.2016.00405
  • Peer Reviewed / Open Access
• [Journal Article] Randomized Phase II Study of Docetaxel plus Personalized Peptide Vaccination versus Docetaxel plus Placebo for Patients with Previously Treated Advanced Wild Type EGFR Non-Small-Cell Lung Cancer. (2016)
  • Author(s): Takayama K, Sugawara S, Saijo Y, Maemondo M, Sato A, Takamori S, Harada T, Sasada T, Kakuma T, Kishimoto J, Yamada A, Noguchi M, Itoh K, Nakanishi Y.
  • Journal Title: J Immunol Res. Volume: 2016 Pages: 1745108-1745108
  • DOI: 10.1155/2016/1745108
  • Peer Reviewed / Open Access
• [Journal Article] がんワクチン療法の進歩 (2016)
  • Author(s): 笹田哲朗
  • Journal Title: Pharma Media （特集）がん免疫療法ー最近の進歩と展望 Volume: 34 (10) Pages: 17-22
• [Journal Article] n Open-Label, Randomized Phase II Trial of Personalized Peptide Vaccination in Patients with Bladder Cancer that Progressed after Platinum-Based Chemotherapy. (2016)
  • Author(s): Noguchi M, Matsumoto K, Uemura H, Arai G, Eto M, Naito S, Ohyama C, Nasu Y, Tanaka M, Moriya F, Suekane S, Matsueda S, Komatsu N, Sasada T, Yamada A, Kakuma T, Itoh K.
  • Journal Title: Clin Cancer Res Volume: 22 Issue: 1 Pages: 54-60
  • DOI: 10.1158/1078-0432.ccr-15-1265
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A randomized phase II clinical trial of personalized peptide vaccination with metronomic low-dose cyclophosphamide in patients with metastatic castration-resistant prostate cancer. (2016)
  • Author(s): Noguchi M, Moriya F, Koga N, Matsueda S, Sasada T, Yamada A, Kakuma T, Itoh K.
  • Journal Title: Cancer Immunol Immunother. Volume: 65 Issue: 2 Pages: 151-60
  • DOI: 10.1007/s00262-015-1781-6
  • Peer Reviewed
• [Journal Article] Phase I study of a new cancer vaccine of ten mixed peptides for advanced cancer patients. (2016)
  • Author(s): Iwasa S, Yamada Y, Heike Y, Shoji H, Honma Y, Komatsu N, Matsueda S, Yamada A, Morita M, Yamaguchi R, Tanaka N, Kawahara A, Kage M, Shichijo S, Sasada T, Itoh K.
  • Journal Title: Cancer Sci. Volume: 印刷中 Issue: 5 Pages: 590-600
  • DOI: 10.1111/cas.12919
  • Peer Reviewed / Open Access
• [Journal Article] Prospect and progress of personalized peptide vaccinations for advanced cancers. (2016)
  • Author(s): Sakamoto S, Noguchi M, Yamada A, Itoh K, Sasada T.
  • Journal Title: Expert Opin Biol Ther. Volume: 16 Issue: 5 Pages: 689-98
  • DOI: 10.1517/14712598.2016.1161752
  • Peer Reviewed
• [Journal Article] 遺伝子変異を標的としたがん免疫療法 (2016)
  • Author(s): 笹田哲朗、大竹淳矢、内山秀美、和田聡、矢田英理香、藤本佑希、吉田慎太郎
  • Journal Title: BIO Clinica Volume: 31 Pages: 102-106
• [Journal Article] Phase I trial of a cancer vaccine consisting of 20 mixed peptides in patients with castrate-resistant prostate cancer: dose-related immune boosting and suppression. (2015)
  • Author(s): Noguchi M, Arai G, Matsumoto K, Naito S, Moriya F, Suekane S, Komatsu N, Matsueda S, Sasada T, Yamada A, Itoh K.
  • Journal Title: Cancer Immunol Immunother. Volume: 64 Issue: 4 Pages: 493-505
  • DOI: 10.1007/s00262-015-1660-1
  • Peer Reviewed
• [Journal Article] Immunological evaluation of peptide vaccination for cancer patients with the HLA-A26 allele. (2015)
  • Author(s): Sakamoto S, Matsueda S, Takamori S, Toh U, Noguchi M, Yutani S, Yamada A, Shichijo S, Yamada T, Suekane S, Kawano K, Sasada T, Hattori N, Kohno N, Itoh K.
  • Journal Title: Cancer Sci. Volume: 106 Issue: 10 Pages: 1257-1263
  • DOI: 10.1111/cas.12757
  • NAID: 120006799352
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of prognostic significance of granulocyte-related factors in cancer patients undergoing personalized peptide vaccination. (2015)
  • Author(s): Sakamoto S, Yoshitomi M, Yutani S, Terazaki Y, Yoshiyama K, Ioji T, Matsueda S, Yamada A, Takamori S, Itoh K, Hattori N, Kohno N, Sasada T.
  • Journal Title: Hum Vaccin Immunother. Volume: 11 Issue: 12 Pages: 2784-9
  • DOI: 10.1080/21645515.2015.1075107
  • NAID: 120006799351
  • Peer Reviewed / Open Access
• [Journal Article] Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients. (2015)
  • Author(s): Araki H, Pang X, Komatsu N, Soejima M, Miyata N, Takaki M, Muta S, Sasada T, Noguchi M, Koda Y, Itoh K, Kuhara S, Tashiro K.
  • Journal Title: Cancer Immunol Immunother. Volume: 64 Issue: 12 Pages: 1565-1573
  • DOI: 10.1007/s00262-015-1756-7
  • Peer Reviewed
• [Journal Article] Phase II Study of Personalized Peptide Vaccination with Both a Hepatitis C Virus-Derived Peptide and Peptides from Tumor-Associated Antigens for the Treatment of HCV-Positive Advanced Hepatocellular Carcinoma Patients. (2015)
  • Author(s): Yutani S, Ueshima K, Abe K, Ishiguro A, Eguchi J, Matsueda S, Komatsu N, Shichijo S, Yamada A, Itoh K, Sasada T, Kudo M, Noguchi M.
  • Journal Title: J Immunol Res. Volume: 2015 Pages: 473909-473909
  • DOI: 10.1155/2015/473909
  • Peer Reviewed / Open Access
• [Journal Article] Feasibility study of personalized peptide vaccination for advanced non-small cell lung cancer patients who failed two or more treatment regimens. (2015)
  • Author(s): Yamada T, Terazaki Y, Sakamoto S, Yoshiyama K, Matsueda S, Komatsu N, Waki K, Yamada A, Kawahara A, Kage M, Sugawara S, Yamashita Y, Sasada T, Takamori S, Itoh K.
  • Journal Title: Int J Oncol. Volume: 46 Issue: 1 Pages: 55-62
  • DOI: 10.3892/ijo.2014.2699
  • Peer Reviewed
• [Journal Article] Personalized Peptide Vaccination for Advanced Colorectal Cancer. (2015)
  • Author(s): Sasada T, Kibe S, Akagi Y, Itoh K.
  • Journal Title: OncoImmunology. Volume: 印刷中 Issue: 5 Pages: e1005512-e1005512
  • DOI: 10.1080/2162402x.2015.1005512
  • Peer Reviewed / Open Access
• [Journal Article] Phase II Study of Personalized Peptide Vaccination for Previously Treated Advanced Colorectal Cancer. (2014)
  • Author(s): Kibe S, Yutani S, Motoyama S, Nomura T, Tanaka N, Kawahara A, Yamaguchi T, Matsueda S, Komatsu N, Miura M, Hinai Y, Hattori S, Yamada A, Kage M, Itoh K, Akagi Y, Sasada T.
  • Journal Title: Cancer Immunol Res. Volume: 2 Issue: 12 Pages: 1154-1162
  • DOI: 10.1158/2326-6066.cir-14-0035
  • Peer Reviewed / Open Access
• [Journal Article] Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients. (2014)
  • Author(s): Takahashi R, Toh U, Iwakuma N, Takenaka M, Otsuka H, Furukawa M, Fujii T, Seki N, Kawahara A, Kage M, Matsueda S, Akagi Y, Yamada A, Itoh K, Sasada T.
  • Journal Title: Breast Cancer Res. Volume: 16 Issue: 4 Pages: 00-00
  • DOI: 10.1186/bcr3685
  • Peer Reviewed / Open Access
• [Journal Article] Feasibility study of personalized peptide vaccination for recurrent ovarian cancer patients. (2014)
  • Author(s): Kawano K, Tsuda N, Matsueda S, Sasada T, Watanabe N, Ushijima K, Yamaguchi T, Yokomine M, Itoh K, Yamada A, Kamura T.
  • Journal Title: Immunopharmacol Immunotoxicol. Volume: 36 Issue: 3 Pages: 224-236
  • DOI: 10.3109/08923973.2014.913617
  • Peer Reviewed / Open Access
• [Journal Article] Personalized Peptide Vaccine for Treatment of Advanced Cancer. (2014)
  • Author(s): Sasada T, Yamada A, Noguchi M, Itoh K.
  • Journal Title: Curr Med Chem. Volume: 21 Issue: 21 Pages: 2332-2345
  • DOI: 10.2174/0929867321666140205132936
  • Peer Reviewed
• [Presentation] High immunogenicity of neoantigens derived from tumor-specific gene mutations. (2016)
  • Author(s): Junya Ohtake, Satoshi Wada, Erica Yada, Yuki Fujimoto, Hidemi Uchiyama, Shintaro Yoshida, Tetsuro Sasada.
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄県宜野湾市
  • Year and Date: 2016-12-06
• [Presentation] Establishment of pancreatic patient-derived xenograft (PDX). (2016)
  • Author(s): Erica Yada, Junya Ohtake, Tetsuro Sasada, Satoshi Wada.
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-10-07
• [Presentation] Comprehensive analysis of T cell responses specific to neoantigens derived from gene mutations. (2016)
  • Author(s): Junya Ohtake, Satoshi Wada, Erica Yada, Yuki Fujimoto, Hidemi Uchiyama, Shintaro Yoshida, Tetsuro Sasada.
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-10-06
• [Presentation] 突然変異遺伝子に対する特異的Ｔ細胞反応の網羅的解析 (2016)
  • Author(s): 大竹淳矢、和田聡、矢田英理香、藤本佑希、内山秀美、吉田慎太郎、笹田哲朗
  • Organizer: 第20回日本がん免疫学会総会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2016-07-28
• [Presentation] 膵臓がんゼノグラフトの有用性の検証 ～治療の新規標的分子の探索に向けて～ (2016)
  • Author(s): 矢田英理香、大竹淳矢、吉田慎太郎、藤本佑希、内山秀美、笹田哲朗、和田聡
  • Organizer: 第20回日本がん免疫学会総会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2016-07-28
• [Presentation] がん免疫療法の現状と今後の展望 (2015)
  • Author(s): 笹田哲朗
  • Organizer: 日本薬物動態学会第30回年会シンポジウム
  • Place of Presentation: タワーホール船堀（東京）
  • Year and Date: 2015-11-14
  • Invited
• [Presentation] Feasibility studies of personalized peptide vaccination for advanced gynecologic cancer patients. (2015)
  • Author(s): Waki K, Kawano K, Sasada T, Ushijima K, ItohK, Kamura T, Yamada A.
  • Organizer: 第74回 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-10-10
• [Presentation] 肝硬変に対する脾摘の生体防御機構に与える影響. (2015)
  • Author(s): 平川雄介、緒方俊郎、笹田哲朗、田中将也、谷口雅彦、鹿毛政義、奥田康司、田中啓之.
  • Organizer: 2015年度日本消化器関連学会週間（JDDW 2015）
  • Place of Presentation: グランドプリンスホテル新高輪（東京）
  • Year and Date: 2015-10-09
• [Presentation] 肝硬変に対する脾摘の生体防御/抗腫瘍免疫機構に与える影響 (2015)
  • Author(s): 平川雄介、緒方俊郎、笹田哲朗、田中将也、谷口雅彦、鹿毛政義、奥田康司、田中啓之.
  • Organizer: 第22回日本門脈圧亢進症学会総会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2015-09-11
• [Presentation] The feasibility of personalized peptide vaccination for previously treated advanced colorectal cancer; A phase II Study. (2015)
  • Author(s): Akagi Y, Kibe S, Yutani S, Motoyama S, Nomura T, Kawahara A, Yamaguchi T, Matsueda S, Komatsu N, Miura M, Hinai Y, Hattori S, Yamada A, Kage M, Itoh K, Sasada T.
  • Organizer: ESSR (European Society for Surgical Research) 2015.
  • Place of Presentation: Liverpool（England）
  • Year and Date: 2015-06-10
  • Int'l Joint Research
• [Presentation] Clinical Significance of Tumor-Associated Tertiary Lymphoid Structures in Pancreatic Cancer. (2015)
  • Author(s): Sasada T, Suekane S, Reinherz EL.
  • Organizer: 13th CIMT (The Association for Cancer Immunotherapy) Annual Meeting.
  • Place of Presentation: Mainz（Germany）
  • Year and Date: 2015-05-11
  • Int'l Joint Research
• [Presentation] Randomized phase II study of personalized peptide vaccination with cyclophosphamide pretreatment in refractory advanced biliary tract cancer patients. (2014)
  • Author(s): Sasada T, Yutani S, Matsueda S, Shirahama T, Yamada A, Itoh K.
  • Organizer: 2014 ASCO Annual Meeting.
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2014-06-01
• [Presentation] Phase II Clinical Trial of Personalized Peptide Vaccination for Previously Treated Advanced Colorectal Cancer. (2014)
  • Author(s): Sasada T, Yutani S, Kibe S, Matsueda S, Komatsu K, Yamada A, Akagi Y, Itoh K.
  • Organizer: 12th CIMT (The Association for Cancer Immunotherapy) Annual Meeting.
  • Place of Presentation: Mainz, Germany
  • Year and Date: 2014-05-06
• [Book] Tumor immunotherapy of esophageal and gastric cancers. (In Rezaei N ed. Cancer Immunology: Immunotherapy for Organ-Specific Tumors.) (2015)
  • Author(s): Toh U, Sasada T, Takahashi R, lwakuma N, Shirouzu K, Itoh K.
  • Total Pages: 485
  • Publisher: Springer-Verlag GmbH
• [Remarks] 神奈川県立がんセンター臨床研究所 がん免疫療法研究開発学部
  • URL: http://kcch.kanagawa-pho.jp/kccri/organization/menekiryoho.html
• [Remarks] 神奈川県立がんセンター がんワクチンセンター
  • URL: http://kcch.kanagawa-pho.jp/outpatient/vaccine.html
• [Remarks] 神奈川県立がんセンター臨床研究所 がん免疫療法研究開発学部
  • URL: http://kcch.kanagawa-pho.jp/kccri/organization/menekiryoho.html
• [Remarks] 神奈川県立がんセンター がんワクチンセンター
  • URL: http://kcch.kanagawa-pho.jp/outpatient/vaccine.html
• [Remarks] 神奈川県立がんセンター臨床研究所 がん免疫療法研究開発学部の研究活動
  • URL: http://kcch.kanagawa-pho.jp/kccri/organization/menekiryoho.html