Development of novel adoptive cell therapy using antigen receptor engineering T cells for chemo/radiotherapy-resistant esophageal cancer

• Project/Area Number: 22791274
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: IMAI Naoko 三重大学, 大学院・医学系研究科, 助教 (30550975)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: がん免疫療法 / T細胞輸注療法 / 抗原受容体改変T細胞 / マルチファンクション性T細胞

Research Abstract

We performed analysis of samples from the clinical trail patients administrated TCR(T cell receptor)-gene transduced lymphocytes and researched on adoptive cell therapy of tumor-specific lymphocytes using mouse model. In the clinical trail patients, TCR-transduced lymphocytes were detected in their peripheral blood as approximately 1% of PBMC. The infused cells have been in vivo persisted in all patients as long as 10 months. In the adoptive cell therapy model of TCR transgenic mouse, presence of CD4+ T cells or integrin signals is elevated CD8+ T cell multifunctionality, and enhanced anti-tumor effect. Furthermore, we have almost established mouse model of the adoptive transfer of TCR-gene transduced lymphocytes.

Research Products

• [Journal Article] T-cellreceptor gene therapy targetingmelanoma-associated antigen-A4 inhibits human tumor growth in non-obesediabetic/SCID/γcnull mice (2012)
  • Author(s): Shirakura Y, Mizuno Y, Wang L, Imai N, Amaike C, Sato E, Ito M, Nukaya I, MinenoJ, Takesako K, Ikeda H, and Shiku H
  • Journal Title: Cancer Sci Volume: vol.103 Pages: 17-25
  • Peer Reviewed
• [Journal Article] T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits human tumor growth in non-obese diabetic/SCID/γc^<null> mice (2012)
  • Author(s): Shirakura Y, Mizuno Y, Wang L, Imai N, Amaike C, Sato E, Ito M, Nukaya I, Mineno J, Takesako K, Ikeda H, Shiku H
  • Journal Title: Cancer Science Volume: 103 Issue: 1 Pages: 17-25
  • DOI: 10.1111/j.1349-7006.2011.02111.x
  • Peer Reviewed
• [Journal Article] CD8^+細胞傷害性T細胞(CTL)の制御によるがん免疫療法 (2010)
  • Author(s): 今井奈緒子、池田裕明、岡本幸子、峰野純一、珠玖洋
  • Journal Title: SURGERY FRONTIER Volume: 17巻 Pages: 263-268
• [Journal Article] 遺伝子改変T細胞・DNAワクチンによるがん治療 (2010)
  • Author(s): 池田裕明、今井奈緒子、珠玖洋
  • Journal Title: 日本臨床増刊号 遺伝子診断学(第2版) Volume: 68巻 Pages: 634-640
• [Journal Article] Novel Strategies for Cell and Gene Therapy of Cancerがんに対する遺伝子改変T細胞輸注療法 (2010)
  • Author(s): 池田裕明、岡本幸子、峰野純一、金井奈緒子、伊藤守、安川正貴、竹迫一任、珠玖洋
  • Journal Title: 臨床血液 Volume: 51巻 Pages: 1647-1653
• [Presentation] T細胞のマルチファンクション性はその生存性と輸注療法の効果を規定する (2011)
  • Author(s): 今井奈緒子、池田裕明、細井勇人、俵功、山根真妃子、王立楠、森和子、日向千咲、珠玖洋
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] インテグリンシグナルを介した教育による効果的なT細胞療法の確立 (2011)
  • Author(s): 細井勇人、池田裕明、日向千咲、王立楠、織戸由貴、今井奈緒子、糠谷育衛、榎竜嗣、峰野純一、竹迫一任、近藤哲、珠玖洋
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-28
• [Presentation] Multifunctionality determines T cellsurvival fate (2011)
  • Author(s): Imai N, Ikeda H, Tawara I, Hosoi H, MoriK, Hyuga C, Yamane M, Wang L, Shiku H
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] Multifunctionality determines T cell survival fate (2011)
  • Author(s): Imai N, Ikeda H, Tawara I, Hosoi H, Mori K, Hyuga C, Yamane M, Wang L, Shiku H
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] In vivo persistence of adoptively transferred TCR gene-modified lymphocytes in patients with advanced esophageal cancer (2011)
  • Author(s): Kageyama S, Ikeda H, Miyahara Y, Hori S, Saito K, Imai N, Okamoto S, Tomura D, Nukaya I, Junichi Mineno J, Takesako K, Katayama N, Shiku H
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] Gene-modified T cell therapy : Harnessing lymphocytes for effective cancer treatment (2011)
  • Author(s): Ikeda H, Imai N, Hosoi H, Yamane M, Okamoto S, Mineno J, Takesako K, Kageyama S, Shiku H
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Antigen receptor gene-modified lymphocytes : harnessing T cells for effective cancer treatment (2011)
  • Author(s): Ikeda H, Imai N, Hosoi H, Yamane M, Okamoto S, Mineno J, Kageyama S, Takesako K, Shiku H
  • Organizer: 第17回日本遺伝子治療学会2011年次学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2011-07-16
• [Presentation] 遺伝子改変T細胞輸注療法 (2011)
  • Author(s): 池田裕明、今井奈緒子、細井勇人、山根真妃子、岡本幸子、峰野純一、竹迫一任、影山慎一、珠玖洋
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2011-06-30
• [Presentation] CD4^+ T細胞が腫瘍特異的CD8^+ T細胞のマルチファンクション性・生存性・抗腫瘍活性に与える影響 (2010)
  • Author(s): 今井奈緒子、池田裕明、山根真妃子、王立楠、珠玖洋
  • Organizer: 第14回日本がん免疫学会学術集会
  • Place of Presentation: 熊本
  • Year and Date: 2010-07-22
• [Presentation] CD8^+細胞傷害性T細胞の制御によるがん免疫療法 (2010)
  • Author(s): 池田裕明、今井奈緒子、岡本幸子、峰野純一、影山慎一、珠玖洋
  • Organizer: 第20回日本サイトメトリー学会学術集会
  • Place of Presentation: 東京(招待講演)
• [Presentation] GENE-MODIFIED LYMPHOCYTES : A TRANSLATIONAL BRIDGE TO EFFECTIVE T CELL THERAPY OF CANCER (2010)
  • Author(s): Ikeda H, Okamoto S, Mineno J, Imai N, Kageyama S, Ito M, Yasukawa M, Takesako K, Shiku H
  • Organizer: 第16回日本遺伝子治療学会総会
  • Place of Presentation: 栃木県総合文化センター(栃木県)(招待講演)
• [Presentation] CD4^+ T cell help on the induction of functional tumor-specific CD8^+ T cells with survival marker. (2010)
  • Author(s): Imai N, Ikeda H, Tawara I, Mori K, Yamane M, Wang L, Shiku H
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸
• [Presentation] 新規STAT3阻害剤は腫瘍局所の免疫抑制状態を解除しT細胞輸注療法の抗腫瘍効果を増強する (2010)
  • Author(s): Sugiyama D, Muraoka D, Imai N, Harada N, Ikeda H, Akiyama Y, Asai A, Shiku H
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 大阪
• [Presentation] CD4^+ T細胞が腫瘍特異的CD8^+ T細胞のマルチファンクション性・生存性・抗腫瘍活性に与える影響 (2010)
  • Author(s): Imai N, Ikeda H, Hosoi H, Yamane M, Wang L, Shiku H
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 大阪
• [Presentation] A novel STAT3 inhibitor reverses tumor-associated immunosuppression and enhances the efficacy of adoptive T cell therapy of cancer (2010)
  • Author(s): Ikeda H, Sugiyama D, Muraoka D, Imai N, Harada N, Akiyama Y, Asai A, Shiku H
  • Organizer: International Society of Biological Therapy of Cancer, Annual Meeting 2010
  • Place of Presentation: 米国、ワシントンDC
• [Presentation] Gene-Modified Lymphocytes : Harnessing T Cells for Effective Cancer Treatment. (2010)
  • Author(s): Ikeda H, Okamoto S, Mineno J, Imai N, Kageyama S, Ito M, Yasukawa M, Takesako K, Shiku H
  • Organizer: International Society for Cellular Therapy, 1^<st> Asia-Pacific Regional Meeting
  • Place of Presentation: 宮崎(招待講演)
• [Presentation] がん特異的T細胞輸注療法の新展開 (2010)
  • Author(s): 池田裕明、今井奈緒子、王立楠、細井勇人、岡本幸子、峰野純一、影山慎一、珠玖洋
  • Organizer: 第31回日本臨床薬理学会年会
  • Place of Presentation: 京都(招待講演)
• [Book] がん生物学イラストレイテッド (2011)
  • Author(s): 今井奈緒子、池田裕明、珠玖洋
  • Publisher: 羊土社
• [Book] がん生物学イラストレイテッド第6章がんと免疫がん抗原 (2011)
  • Author(s): 今井奈緒子、池田裕明、珠玖洋
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.shikuken.jp
• [Remarks]
  • URL: http://www.shikuken.jp
• [Remarks]
  • URL: http://www.shikuken.jp