Analysis of immune-responses as antigen spreading in patients treated with cancer immunotherapy

• Project/Area Number: 20790950
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: KITANO Shigehisa Mie University, 大学院・医学系研究科, 助教 (60402682)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腫瘍免疫学 / 臨床腫瘍学 / 癌免疫療法 / 腫瘍学

Research Abstract

A phase I clinical trial of CHP-HER2 complex vaccine with GM-CSF was carried out. In some patients not only HER2 specific T cell immune responses but also MAGE-A4 specific T cell responses was detected, suggesting antigen spreading triggered by the vaccination with CHP-HER2. Though these data are based on a small phase I study and should be cautiously interpreted, patients induced immune responses had shown no disease progression for longer periods (range, 9-40 month) compared to no responders (range, 2-10 month).

Research Products

• [Journal Article] Antibody responses against NY-ESO-1 and HER2 antigens inpatients vaccinated with combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432. (2009)
  • Author(s): Aoki M., Ueda S., Hirayama M., Nishikawa H., Kitano S., Ikeda H., Toyoda H., Tanaka K., Kanai K., Takabayashi A., Imai H., Shiraishi T., Sato E., Wada H., Nakayama E., Takei Y., Katayama N., Shiku H., Kageyama S.
  • Journal Title: Vaccine (in press, peer reviewed)
• [Journal Article] Rapid αβTCR-mediated responses in gamma delta T cells transduced with cancer-specific TCR genes. (2009)
  • Author(s): Hiasa A., Nishikawa H., Hirayama M., Kitano S., Okamoto S., Chono H., Yu S.S., Mineno J., Tanaka Y., Minato N., Kato I. Shiku H.
  • Journal Title: Gene Therapy 16(peer reviewed) Pages: 620-628
• [Journal Article] Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432 (2009)
  • Author(s): Aoki M., Ueda S., Hirayama M., Nishikawa H., Kitano S., Ikeda H., Toyoda H., Tanaka K., Kanai K., Takabayashi A., Imai H., Shiraishi T., Sato E., Wada H., Nakayama E., Takei Y., Katayama N., Shiku H., Kageyama S.
  • Journal Title: Vaccine (In press)
  • Peer Reviewed
• [Journal Article] Elevated Fibrin-Related Markers in Patients with Malignant Diseases Suspected of Having Thrombotic Disorders. (2009)
  • Author(s): Nomura H., Wada H., Mizuno T., Yamashita Y., Saito K., Kitano S., Katayama N., Yamada N., Sugiyama T., Sudo A., Usui M., Isaji S., Nobori T.
  • Journal Title: Clinical and Applied Thrombosis/Hemostasis (In press)
  • Peer Reviewed
• [Journal Article] Rapid αβ TCR-mediated responses in gamma delta T cells transduced with cancer-specific TCR genes. (2009)
  • Author(s): Hiasa A, Nishikawa H, Hirayama M, Kitano S, Okamoto S, Chono H, Yu SS, Mineno J, Tanaka Y, Minato N, Kato I, Shiku H.
  • Journal Title: Gene Therapy. 16 Pages: 620-628
  • Peer Reviewed
• [Journal Article] Deletion of chromosome arm 15q in a case of minimally differentiated hypoplastic AML-M0. (2008)
  • Author(s): Fujieda A., Masuya M., Kitano S., Miyazaki K., Yazaki A., Sugimoto Y., Usui E., Miyata E., Shibasaki T., Yamamura K., Ohishi K., Nishii K, Nakase K., Takeuchi T. Katayama N.
  • Journal Title: Cancer Genetics and Cytogenetics 184(1)(peer reviewed) Pages: 57-61
• [Journal Article] Long-term phenotypic, functional and genetic stability of cancer-specific T-cell receptor (TCR)αβgenes transduced to CD8+ T cells. (2008)
  • Author(s): Hiasa A., Hirayama M., Nishikawa H., Kitano S., Nukaya I., Yu SS., Mineno J., Kato I., Shiku H.
  • Journal Title: Gene Therapy 15(peer reviewed) Pages: 695-699
• [Journal Article] Humoral immune responses in patients vaccinated with 1-146 HER2 protein complexed with cholesteryl pullulan nanogel. (2008)
  • Author(s): Kageyama S., Kitano S., Hirayama M., Nagata Y., Imai H., Shiraishi T., Akiyoshi K., Scott AM., Murphy R., Hoffman EW., Old LJ., Katayama N., Shiku H.
  • Journal Title: Cancer Sci. 99(3)(peer reviewed) Pages: 601-607
  • NAID: 10024004079
• [Journal Article] Humoral immune responses in patients vaccinated with 1-146 HER2 protein complexed with cholesteryl pullulan nanogel (2008)
  • Author(s): Kageyama S., Kitano S., Hirayama M., Nagata Y., Imai H., Shiraishi T., Akiyoshi K., Scott AM., Murphy R., Hoffman EW., Old LJ., Katayama N., Shiku H.
  • Journal Title: Cancer Science 99(3) Pages: 601-607
  • NAID: 10024004079
  • Peer Reviewed
• [Journal Article] Long-term phenotypic, functional and genetic stability of caneer-specific T-cell receptor (TCR) αβ genes transduced to CD8^+ T cells (2008)
  • Author(s): Hiasa A., Hirayama M., Nishikawa H., Kitano S., Nukaya I., Yu SS., Mineno J., Kato I. and Shiku H.
  • Journal Title: Gene Therapy 15 Pages: 695-699
  • Peer Reviewed
• [Journal Article] Deletion of chromosome arm 15q in a case of minimally dlifferentiated hypoplastic AML-M0 (2008)
  • Author(s): Fujieda A., Masuya M., Kitano S., Miyazaki K., Yazaki A., Sugimoto Y., Usui E., Miyata E., Shibasaki T., Y amamura K., Ohishi K., Nishii K, Nakase K., Takeuchi T. and Katayama N.
  • Journal Title: Cancer Genetics and Cytogenetics 184(1) Pages: 57-61
  • Peer Reviewed
• [Presentation] Skeletal metastases in gastric cancer:analysis of skeletal-related events and plasma endothelin-1. (2009)
  • Author(s): Mizuno T., Nomura H., Saito K., Yamashita Y., Kitano S., Miyata E., Tamaru S., Hiasa A., Kageyama S., Katayama N.
  • Organizer: ESMO annual meeting.
  • Place of Presentation: Berlin, Germany.
• [Presentation] 教育講演(パネリスト) (2009)
  • Author(s): 北野滋久
  • Organizer: 第6回日本乳癌学会中部地方会
  • Place of Presentation: 浜松
• [Presentation] 化学療法中の胃腸薬の意義について (2009)
  • Author(s): 北野滋久、水野聡朗、斉藤佳菜子、山下芳樹、日浅厚則、影山慎一、片山直之
  • Organizer: 第17回日本乳癌学会学術総会
  • Place of Presentation: 浜松
• [Presentation] 脳転移を契機にHER2の変化を確認できた再発乳癌の二例 (2009)
  • Author(s): 斉藤佳菜子、水野聡朗、北野滋久、山下芳樹、日浅厚則、影山慎一、花村典子、小川朋子、伊佐治秀司
  • Organizer: 第17回日本乳癌学会学術総会
  • Place of Presentation: 東京
• [Presentation] 教育セミナー症例検討(パネリスト) (2009)
  • Author(s): 北野滋久
  • Organizer: 第6回日本乳癌学会中部地方会
  • Place of Presentation: 浜松
• [Presentation] Skeletal metastases in gastric cancer : analysis of skeletal-related events and plasma endothelin-1 (2009)
  • Author(s): Mizuno T., Nomura H., Saito K., Yamashita Y., Kitano S., Miyata E., Tamaru S., Hiasa A., Kageyama S., Katayama N.
  • Organizer: ESMO annual Meeting
  • Place of Presentation: Berlin, Germany
• [Presentation] Combination cancer vaccine of CHP-NY-ESO-1 and CHP-HER2 with immuno-adjuvant, OK-432, for chemorefractory metastatic or recurrent esophageal cancer patients. (2008)
  • Author(s): Ueda S., Aoki M., Nishikawa H., Hirayama M., Kitano S., Hayashi E., Kanai M., Takabayashi A., Shiku H., Kageyama S.
  • Organizer: 99th AACR Annual Meeting.
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Rapid αβTCR-mediated responses inγδT cells transduced with cancer-specific TCR. (2008)
  • Author(s): Hiasa A., Nishikawa H., Hirayama M., Kitano S., Nakayama E., Okamoto S., Chono H., Yu S.S., Mineno, J., Tanaka Y., Minato N., Kato I., Shiku H.
  • Organizer: 99th AACR Annual Meeting.
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Functional analyses of T cells transduced with MAGE-A4-specificαβtype TCR genes. (2008)
  • Author(s): Hirayama M., Hiasa A., Nishikawa H., Shirakura Y., Ikeda H., Kitano S., Tajima K., Nukaya I., Yu S.S., Mineno J., Ito M., Kato I., Shiku H.
  • Organizer: 99th AACR Annual Meeting.
  • Place of Presentation: San Diego, CA, USA
• [Presentation] 原発不明癌に対するドセタキセル/カルボプラチン併用療法の検討. (2008)
  • Author(s): 北野滋久、水野聡朗、斉藤佳菜子、野村英樹、宮田恵理、田丸智巳、日浅厚則、中瀬一則、影山慎一、片山直之
  • Organizer: 第6回日本臨床腫瘍学会
  • Place of Presentation: 福岡
• [Presentation] Combination cancer vaccine of CHP-NY-ESO-1 and CHP-HER 2 with immuno-adjuvant, OK-432, for chemorefractory metastatic or recurrent esophageal cancer patients 99th AACR Annual Meeting (2008)
  • Author(s): Ueda S., Aoki M., Nishika wa H., Hirayama M., Kitano S., Hayashi E., Kanai M., Takabayashi A., Shiku H., and Kageyama S.
  • Organizer: 99th AACR Annual Meeting
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Rapid αβ TCR-mediated responses in γδ T cells transduced with cancer-specific TCR (2008)
  • Author(s): Hiasa A., Nishikawa H., Hirayama M., Kitano S., Nakayama E., Okamoto S., Chono H., Yu S.S., Mineno, J., Tanaka Y., Minato N., Kato I., and Shiku H.
  • Organizer: 99th AACR Annual Meeting
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Functional analyses of T cells transduced with MAGE-A4-specific αβ type TCR genes (2008)
  • Author(s): Hirayama M., Hiasa A., Nishikawa H., Shirakura Y., Ikeda H., Kitano S., Tajima K., Nukaya I., Yu S. S., Mineno J., Ito M., Kato I., and Shiku H.
  • Organizer: 99th AACR Annual Meeting
  • Place of Presentation: San Diego, CA, USA
• [Presentation] Large scale T-cell expansion of cancer patients by using retronectin co-stimulation method for adoptive T-cell therapy (2008)
  • Author(s): Ideno M., Muraki N., Kato A., Enoki R., Kitano S., Ikeda H., Kageyama S., Shiku H., Kato I.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Safety and immune responses of combination cancer vaccines of CHP-NY-ESO-1 and CHP-HER2 for esoshageal cancer patients (2008)
  • Author(s): Aoki M., Ueda S., Nishikawa H., Hirayama M., Kitano S., Ikeda H., Kanai M., Takabayashi A., Sato E., Takei Y., Naoyuki K., Shiku H., Kageyama S.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 術前化学療法AC followed by Weekly Paclitaxelの検討 (2008)
  • Author(s): 斎藤佳菜子、水野聡朗、北野滋久、田丸智し、日浅厚則、影山慎一
  • Organizer: 第16回日本乳癌学会総会
  • Place of Presentation: 大阪
• [Presentation] 当院での進行乳癌Triple Negative (TN)症例の検討 (2008)
  • Author(s): 北野滋久、水野聡朗、斉藤佳菜子、宮田恵理、田丸智巳、日浅厚則、中瀬一則、影山慎一、片山直之
  • Organizer: 第46回日本癌治療学会総会
  • Place of Presentation: 名古屋
• [Presentation] 乳癌術後AC療法における制吐剤デキサメサゾンの投与量の検討 (2008)
  • Author(s): 宮田恵里、水野聡朗、斉藤佳菜子、北野滋久、野村英毅、田丸智巳、日浅厚則、影山慎一、中瀬一則、片山直之
  • Organizer: 第46回日本癌治療学会総会
  • Place of Presentation: 名古屋
• [Presentation] 前治療歴を有する転移性乳癌に対するビノレルビン単独療法の検討 (2008)
  • Author(s): 田丸智巳、水野聡朗、斎藤佳菜子、北野滋久、野村英毅、宮田恵里、日浅厚則、中瀬一則、影山慎一、片山直之
  • Organizer: 第46回日本癌治療学会総会
  • Place of Presentation: 名古屋
• [Presentation] 当院における早期乳癌に対する術後TC療法の検討 (2008)
  • Author(s): 斎藤佳菜子、水野聡朗、北野滋久、宮田恵理、田丸智巳、日浅厚則、影山慎一、中瀬一則、片山直之
  • Organizer: 第46回日本癌治療学会総会
  • Place of Presentation: 名古屋
• [Presentation] CPT-11単独療法が奏効したDIC合併の進行胃癌の1例 (2008)
  • Author(s): 山下芳樹、野村英毅、水野聡朗、斉藤佳菜子、北野滋久、宮田恵里、田丸智巳、日浅厚則、影山慎一、中瀬一則、片山直之
  • Organizer: 第46回日本癌治療学会総会
  • Place of Presentation: 名古屋