Optimization of cancer vaccine that are combined with TCR-gene transduced T cell transfer for esophageal cancer

• Project/Area Number: 15K10093
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: Kageyama Shinichi 三重大学, 医学系研究科, 教授 (80194695)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: がんワクチン / 食道癌 / 複合的がん免疫療法 / TCR遺伝子導入細胞療法 / 免疫モニタリング

Outline of Final Research Achievements

Serum and lymphocytes samples were collected and stored for this exploratory clinical research. We performed ELISA analysis (serum) targeting cancer-testis antigen protein of MAGE-A4, NY-ESO-1, and collected these data.
In the analysis of CHP-MAGE-A4 cancer vaccine, it was revealed that the prognosis was poor in patients with NY-ESO-1-expression on the tumor tissue and the pre-existing antibody responses.
Comparative data were obtained for optimization of the cancer vaccine design to be used concomitantly in TCR-gene transduced T cell transfer.

Research Products

• [Journal Article] Clinical Implications of CD4+CD25+Foxp3+Regulatory T Cell Frequencies After CHP-MAGE-A4 Cancer Vaccination (2018)
  • Author(s): Wada M, Tsuchikawa T, Kyogoku N, Abiko T, Miyauchi K, Takeuchi S, Kuwatani T, Shichinohe T, Miyahara Y, Kageyama S, Ikeda H, Shiku H, Hirano S
  • Journal Title: Anticancer Res Volume: 38 Pages: 1435-1444
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serum immunoglobulin E response as a marker for unfavorable prognosis following cholesteryl pullulan-MAGE A4 vaccination (2018)
  • Author(s): Abiko Takehiro、Tsuchikawa Takahiro、Miyauchi Kengo、Wada Masataka、Kyogoku Noriaki、Shichinohe Toshiaki、Miyahara Yoshihiro、Kageyama Shinichi、Ikeda Hiroaki、Shiku Hiroshi、Hirano Satoshi
  • Journal Title: Oncology Letters Volume: 15 Pages: 3703-3711
  • DOI: 10.3892/ol.2018.7767
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cancer immunotherapy using gene-engineered T cells (2018)
  • Author(s): 影山 愼一
  • Journal Title: Rinsho Ketsueki Volume: 59 Issue: 2 Pages: 216-224
  • DOI: 10.11406/rinketsu.59.216
  • NAID: 130006441932
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Safety and persistence of WT1-specific T-cell receptor gene-transduced lymphocytes in patients with AML and MDS. (2017)
  • Author(s): Tawara I, Kageyama S, Miyahara Y, Fujiwara H, Nishida T, Akatsuka Y, Ikeda H, Tanimoto K, Terakura S, Murata M, Inaguma Y, Masuya M, Inoue N, Kidokoro T, Okamoto S, Tomura D, Chono H, Nukaya I, Mineno J, Naoe T, Emi N, Yasukawa M, Katayama N, Shiku H.
  • Journal Title: Blood Volume: 130 Issue: 18 Pages: 1985-1994
  • DOI: 10.1182/blood-2017-06-791202
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic Risk Factors Associated With Antiemetic Efficacy of Palonosetron, Aprepitant, and Dexamethasone in Japanese Breast Cancer Patients Treated With Anthracycline-based Chemotherapy (2017)
  • Author(s): Yokoyama S, Tamaru S, Tamaki S, Nakanishi D, Mori A, Yamakawa T, Ao T, Sakata Y, Mizuno T, Iwamoto T, Watanabe K, Simomura M, Kawakami K, Konishi N, Kageyama S, Ohtani S, Yamada T, Ban S, Ooi K
  • Journal Title: Clin Breast Cancer Volume: S1526-8209 Issue: 2 Pages: 507-511
  • DOI: 10.1016/j.clbc.2017.05.013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Attempt to Harvest a Sufficient Number of Mononuclear Cells in an Appropriate Blood Product Volume By Modification of the Default Apheresis Setting. (2017)
  • Author(s): Tanaka Y, Ohishi K, Sawai T, Iwasaki H, Kageyama S, Masuya M, Matsumoto T, Tanigawa T, Wada H, Shiku H, Ito M, Katayama N
  • Journal Title: Ther Apher Dial. Volume: 21 Issue: 5 Pages: 507-511
  • DOI: 10.1111/1744-9987.12562
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel. (2016)
  • Author(s): Kyogoku N, Ikeda H, Tsuchikawa T, Abiko T, Fujiwara A, Maki T, Yamamura Y, Ichinokawa M, Tanaka K, Imai N, Miyahara Y, Kageyama S, Shiku H, Hirano S.
  • Journal Title: Oncology Letters Volume: 12 Issue: 6 Pages: 4493-4504
  • DOI: 10.3892/ol.2016.5253
  • NAID: 120005981404
  • Peer Reviewed / Open Access
• [Journal Article] Clinical relevance of antigen spreading pattern induced by CHP-MAGE-A4 cancer vaccination (2016)
  • Author(s): Miyauchi K, Tsuchikawa T, Wada M, Abiko T, Kyogoku N, Shichinohe T, Miyahara Y, Kageyama S, Ikeda H, Shiku H, Hirano S.
  • Journal Title: Immunotherapy Volume: 印刷中 Issue: 5 Pages: 527-40
  • DOI: 10.2217/imt-2016-0007
  • Peer Reviewed
• [Journal Article] 2015 Guidance on cancer immunotherapy development in early-phase clinical studies (2015)
  • Author(s): Guidance Development Review Committee; Working Group for Clinical Studies of Cancer Immunotherapy; Working Group for Effector Cell Therapy; Working Group for CMC/Non-clinical Studies; Working Group for Cancer Vaccines and Adjuvants; Working Group for Anti-immune Checkpoint Therapy and Comprehensive Cancer
  • Journal Title: Cancer Sci Volume: 106 Issue: 12 Pages: 1761-1771
  • DOI: 10.1111/cas.12819
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Adoptive transfer of MAGE-A4 T-cell receptor gene-transduced lymphocytes in patients with recurrent esophageal cancer (2015)
  • Author(s): Kageyama S, Ikeda H, Miyahara Y, Imai N, Ishihara M, Saito K, Sugino S, Ueda S, Ishikawa T, Kokura S, Naota H, Ohishi K, Shiraishi T, Inoue N, Tanabe M, Kidokoro T, Yoshioka H, Tomura D, Nukaya I, Mineno J, Takesako K, Katayama N, Shiku H.
  • Journal Title: Clinical Cancer Research Volume: in press Issue: 10 Pages: 2268-2277
  • DOI: 10.1158/1078-0432.ccr-14-1559
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Cytokine Release Syndrome and Tumor Responses in a First-in-Man Trial of a Novel Affinity-Enhanced TCR-Gene Transduced T Cell Transfer Targeting NY-ESO-1 Antigen (2017)
  • Author(s): 影山 愼一
  • Organizer: 59th ASH Annual Meeting & Exposition 第59回米国血液学会総会
  • Int'l Joint Research
• [Presentation] Clinical trials of adoptive transfer of TCR-modified T cell therapy for refractory cancer (2017)
  • Author(s): 影山 愼一
  • Organizer: 8th Annual Meeting of Asian Cellular Therapy Organization 第8回アジア細胞療法学会
  • Int'l Joint Research / Invited
• [Presentation] 食道癌に対するがんワクチンとT細胞療法の臨床試験 (2017)
  • Author(s): 影山 愼一
  • Organizer: 第15回日本臨床腫瘍学会学術集会
  • Invited
• [Presentation] MAGE-A4及びNY-ESO-1抗原特異的 TCR遺伝子改変T細胞輸注療法の臨床試験 (2017)
  • Author(s): 影山 愼一
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 治療抵抗性固形腫瘍を対象とした NY-ESO-1及びMAGE-A4を標的にするTCR遺伝子導入 T細胞輸注療法の臨床試験 (2017)
  • Author(s): 影山 愼一
  • Organizer: 第23回日本遺伝子細胞治療学会学術集会
  • Invited
• [Presentation] 食道癌に対する免疫療法：がんワクチンと免疫細胞治療 (2016)
  • Author(s): 影山愼一
  • Organizer: 第70回日本食道学会学術集会
  • Place of Presentation: ザ・プリンス パークタワー東京（東京都・港区）
  • Invited
• [Presentation] 滑膜肉腫に対するTCR改変T細胞を用いた 免疫細胞輸注療法 (2015)
  • Author(s): 影山愼一 松峯昭彦
  • Organizer: 第53回日本癌治療学会学術総会
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2015-10-31
  • Invited
• [Book] Immunotyerapy of Cancer（分担） (2016)
  • Author(s): Shinichi Kageyama
  • Total Pages: 358
  • Publisher: Springer
• [Remarks] 三重大学大学院遺伝子・免疫細胞治療学 研究活動
  • URL: http://www.shikuken.jp/