The combination effects of conventional chemotherapy and adoptive cell therapy for refractory advanced/recurrent cancer

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591581
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kurume University
• Principal Investigator: TOH Uhi Kurume University, 医学部, 講師 (60268901)
• Co-Investigator(Kenkyū-buntansha): YAMANA Hideaki 久留米大学, 医学部, 教授 (30140669) ; SEKI Naoko 久留米大学, 医学部, 講師 (40226634)
• Project Period (FY): 2008 – 2010
• Keywords: 細胞免疫療法 / 化学療法 / 難治性がん / Trastuzumab / Bortezomib

Research Abstract

Adoptive cell therapy (ACT) could successfully treat a limited part of patients inducing tumor regression or prolonged survival, but therapeutic efficacy was still lower than expected in most of the patients. For the further clinical application, development of more effective multidisciplinary cancer therapy including ACT therapy combined with chemotherapeutic agents or molecular targeting therapeutics has been focused in our studies. Therapeutic strategies and the mechanisms of biological effects have been studied in vitro and several clinical trials. The data show that combination therapy of CTL transfer and chemotherapy is a feasible option for patients with refractory lung, breast and gastric cancer without serious adverse events. Our preliminary data also suggest that in the ability of DC cross-presentation followed by the enhancement of antitumor cellular immunity by trastuzumab. Moreover, we demonstrated that bortezomib sensitizes human various cancer cells to TRAIL-mediated apoptosis via activation of both extrinsic and intrinsic apoptosis pathways.

Research Products

• [Journal Article] Bortezomib sensitizes human esophageal squamous cell carcinoma cells to TRAIL-mediated apoptosis via activation of both extrinsic and intrinsic apoptosis pathways. (2010)
  • Author(s): Seki N, Toh U, Sayers TJ, Fujii T, Miyagi M, Akagi Y, Kusukawa J, Kage M, Shirouzu K, Yamana H.
  • Journal Title: Mol Cancer Ther. 9(6) Pages: 1842-51
  • Peer Reviewed
• [Journal Article] YB-1 prevents apoptosis via the mTOR/STAT3 pathway in HER-2-overexpressing breast cancer cells. (2009)
  • Author(s): Fujii T, Seki N, Takahashi H, Inoue Y, Toh U, Kage M, Shirouzu K.
  • Journal Title: Future Oncol. 5(2) Pages: 153-6
• [Journal Article] Cell-cycle regulation by protein kinase C and mitogen-activated protein kinase signaling in breast cancer cells (2009)
  • Author(s): Teruhiko Fujii, Anna Nakamura, Hiroki Takahashi, Roka Namoto Matsubayashi, Yuka Inoue, Miki Takenaka, Nobutaka Iwakuma, Hiroko Otsuka, Uhi Toh, Hideaki Yamana, Masayoshi Kage, Kazuo Shirouzu
  • Journal Title: Current Topices in Biochemical Research 11(2) Pages: 1-11
• [Journal Article] Preclinical studies of molecular-targeting diagnostic and therapeutic strategies against breast cancer. (2008)
  • Author(s): Fujii T, Yokoyama G, Takahashi H, Namoto R, Nakagawa S, Toh U, Kage M, Shirouzu K, Kuwano M.
  • Journal Title: Breast Cancer 15(1) Pages: 73-8
  • Peer Reviewed
• [Journal Article] Preclinical and clinical studies of novel breast cancer drugs targeting molecules involved in protein kinase C signaling, the putative metastasis-suppressor gene Cap43 and the Y-box binding protein-1. (2008)
  • Author(s): Fujii T, Yokoyama G, Takahashi H, Toh U, Kage M, Ono M, Shirouzu K, Kuwano M.
  • Journal Title: Curr Med Chem. 15(6) Pages: 528-37
  • Peer Reviewed
• [Presentation] 難治性進行再発乳癌に対するテーラーメイド癌ペプチドワクチン療法による集学的治療 (2010)
  • Author(s): 唐宇飛、白水和雄、伊東恭悟
  • Organizer: 第18回日本乳癌学会学術総会
  • Year and Date: 20100000
• [Presentation] 実地臨床から見る難知性固形癌に対する細胞免疫療法及びペクチドワクチン療法の可能性 (2010)
  • Author(s): 唐宇飛、山名秀明、伊東恭悟、白水和雄
  • Organizer: 第48回日本癌治療学会学術集会
  • Year and Date: 20100000
• [Presentation] テーラーメイドがんペプチドワクチンによる難治性乳がんの新規集学的治療 (2010)
  • Author(s): 唐宇飛、岩熊伸高、竹中美貴、大塚弘子、高橋龍司、白水和雄、山名秀明、伊東恭悟
  • Organizer: 第72回日本臨床外科学会総会
  • Year and Date: 20100000
• [Presentation] 臨床的見地から見る難知固形癌に対する細胞免疫療法及びペプチドワクチン療法の有効性 (2010)
  • Author(s): 唐宇飛、岩熊伸高、竹中美貴、大塚弘子、高橋龍司、山名秀明、伊東恭悟、白水和雄
  • Organizer: 第23回日本バイオセラピィ学会学術集会総会
  • Year and Date: 20100000
• [Presentation] 乳癌組織におけるFOXP3とpSTAT3の発現についての検討 (2010)
  • Author(s): 竹中美貴、唐宇飛、関直子、岩熊伸高、大塚弘子、白水和雄、山名秀明、鹿毛政義
  • Organizer: 第23回日本バイオセラピィ学会学術集会総会
  • Year and Date: 20100000
• [Presentation] A phase II study of personalized selection of peptide vaccines combined with conventional chemo- or endocrine therapy for refractory breast cancer (2010)
  • Author(s): 唐宇飛
  • Organizer: American Society of Clinical Oncology (ASCO) Annual 2010 Meeting
  • Year and Date: 2010-06-07
• [Presentation] 難治性固形癌に対する標準化学治療薬と細胞免疫療法との併用療法の可能性 (2009)
  • Author(s): 唐宇飛
  • Organizer: 第6回日本免疫治療学会研究会(JRAI)学術集会
  • Year and Date: 20090000
• [Presentation] 基礎解析から見た治療耐性進行再発癌に対する細胞免疫療法を含めた集学的治療の可能性 (2009)
  • Author(s): 唐宇飛、関直子、福永真理、福嶋敬愛、三島麻衣、山名秀明、白水和雄
  • Organizer: 第109回日本外科学会定期学術集会
  • Year and Date: 20090000
• [Presentation] 抗体治療薬Trastuzumabによる乳癌特異的抗腫瘍細胞性免疫の誘導 (2009)
  • Author(s): 唐宇飛、三島麻衣、福永真理、福嶋敬愛、白水和雄、山名秀明、淡河恵津世、藤井輝彦
  • Organizer: 第17回日本乳癌学会学術総会
  • Year and Date: 20090000
• [Presentation] 抗体治療薬投与による特異的抗腫瘍細胞性免疫の誘導に関する検討 (2009)
  • Author(s): 唐宇飛、福嶋敬愛、山名秀明、白水和雄
  • Organizer: 第64回日本消化器外科学会総会
  • Year and Date: 20090000
• [Presentation] 標準化学療法治療薬と細胞免疫療法との併用による相乗(加)的抗腫瘍効果についての検討 (2009)
  • Author(s): 唐宇飛、福永真理、福永敬愛、大塚弘子、山名秀明、藤井輝彦、白水和雄
  • Organizer: 第47回日本癌治療学会学術集会
  • Year and Date: 20090000
• [Presentation] The combination therapy of trastuzumab and adoptive cell therapy for refractory breast cancer (2009)
  • Author(s): U Toh, K Shirouzu
  • Organizer: Internstional Surgical Week 2009
  • Year and Date: 20090000
• [Presentation] Induction of specific anti-cancer immune response by trastuzumab administration in patients with advanced breast cancer (2009)
  • Author(s): Hiroko Otsuka, Uhi Toh, Mari Fukunaga, Takanaru Fukushima, Teruhiko Fujii, Kazuo Shirouzu
  • Organizer: Global Breast Cancer Conference 2009
  • Year and Date: 20090000
• [Presentation] The combination therapy of trastuzumab and adoptive cell therapy for refractory breast cancer (2009)
  • Author(s): 唐宇飛
  • Organizer: World Cancer Congress 2010 Tri-Breast Cancer conference
  • Year and Date: 20090000
• [Presentation] Strategy to augment the efficacy of immunotherapy for refractory breast cancer : a pilot clinical study of adoptive cell therapy combined with trastuzumab (2009)
  • Author(s): N Seki, U Toh, T.Fujii, S Nagagawa, K Shirouzu, H Yamana
  • Organizer: European Breast Cancer Conference 7
  • Year and Date: 20090000
• [Presentation] プロテアソーム阻害薬によるTRAIL感受性の増強効果 (2008)
  • Author(s): 唐宇飛、藤井輝彦、白水和雄、関直子、山名秀明
  • Organizer: 第29回癌免疫外科研究会
  • Year and Date: 20080000
• [Presentation] Trastuzumab併用細胞免疫療法による難治性乳癌の集学的治療 (2008)
  • Author(s): 唐宇飛、藤井輝彦、矢原敏郎、中川志乃、三島麻衣、福永真理、淡河恵津世、白水和雄
  • Organizer: 第16回日本乳癌学会学術総会
  • Year and Date: 20080000
• [Presentation] 難治性乳癌の抗体治療薬併用細胞免疫療法に関する検討 (2008)
  • Author(s): 福嶋敬愛、唐宇飛、三島麻衣、福永真理、白水和雄、関直子、山名秀明
  • Organizer: 第21回日本バイオセラピィ学会学術集会総会
  • Year and Date: 20080000
• [Presentation] Trastuzumabによる腫瘍特異的細胞性免疫の誘導 (2008)
  • Author(s): 唐宇飛、関直子、山名秀明、白水和雄
  • Organizer: 第21回日本バイオセラピィ学会学術集会総会
  • Year and Date: 20080000
• [Presentation] Strategy to augment the efficacy of immunotherapy for refractory breast cancer using trastuzumab combined adoptive cell therapy (2008)
  • Author(s): 唐宇飛
  • Organizer: 2008 ASCO Annual Meeting
  • Year and Date: 20080000
• [Remarks] ホームページ等