Development of new immunotherapy for resistant ovarian cancer to immunecheckpoint blockade therapy

• Project/Area Number: 15H06881
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: National Cancer Center Japan
• Principal Investigator: IWAMA Tatsuaki 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (90757600)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 婦人科 / 外科 / がん / 免疫 / ワクチン

Outline of Final Research Achievements

Although vaccine-induced glypican-3 (GPC3)-peptide-specific cytotoxic T lymphocytes (CTLs) were often tumor reactive in vitro and were correlated with overall survival, no complete response was observed. In the current study, we synthesized liposome-coupled GPC3-derived CTL epitope peptide (pGPC3-lipsome) and investigated its antitumor potential. Vaccination with pGPC3-liposome induced peptide-specific CTLs at a lower dose than conventional peptide vaccine emulsified in incomplete Freund’s adjuvant. Coupling of pGPC3 to liposomes was essential for effective priming of GPC3-specific CTLs. In addition, immunization with pGPC3-liposome inhibited GPC3-expressing tumor growth. Thus, vaccination with tumor-associated antigen-derived epitope peptides coupled to the surfaces of liposomes may be a novel therapeutic strategy for cancer.

Research Products

• [Journal Article] Vaccination with liposome-coupled glypican-3-derived epitope peptide stimulates cytotoxic T lymphocytes and inhibits GPC3-expressing tumor growth in mice. (2016)
  • Author(s): Iwama T, Uchida T, Sawada Y, Tsuchiya N, Sugai S, Fujinami N, Shimomura M, Yoshikawa T, Zhang R, Uemura Y, Nakatsura T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 469(1) Issue: 1 Pages: 138-43
  • DOI: 10.1016/j.bbrc.2015.11.084
  • Peer Reviewed / Open Access
• [Journal Article] Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Va24 Invariant NK T-like Cells from Human Induced Pluripotent Stem Cells (2016)
  • Author(s): Kitayama S, Zhang R, Liu TY, Ueda N, Iriguchi S, Yasui Y, Kawai Y, Tatsumi M, Hirai N, Mizoro Y, Iwama T, Watanabe A, Nakanishi M, Kuzushima K, Uemura Y, Kaneko S
  • Journal Title: Stem Cell Reports Volume: 6 Issue: 2 Pages: 213-227
  • DOI: 10.1016/j.stemcr.2016.01.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatocellular carcinoma cell sensitivity to Vg9Vd2 T lymphocyte-mediated killing is increased by zoledronate. (2016)
  • Author(s): Sugai S, Yoshikawa T, Iwama T, Tsuchiya N, Ueda N, Fujinami N, Shimomura M, Zhang R, Kaneko S, Uemura Y, Nakatsura T.
  • Journal Title: Int J Oncol. Volume: 48 (5) Issue: 5 Pages: 1794-1804
  • DOI: 10.3892/ijo.2016.3403
  • Peer Reviewed / Open Access
• [Journal Article] BCR-ABL-specific CD4+ T-helper cells promote the priming of antigen-specific cytotoxic T cells via dendritic cells (2016)
  • Author(s): Ueda N, Zhang R, Tatsumi M, Liu TY, Kitayama S, Yasui Y, Sugai S, Iwama T, Senju S, Okada S, Nakatsura T, Kuzushima K, Kiyoi H, Naoe T, Kaneko S, Uemura Y.
  • Journal Title: Cell Mol Immunol. Volume: - Issue: 1 Pages: 15-26
  • DOI: 10.1038/cmi.2016.7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhancement of antitumor effect by peptide vaccine therapy in combination with anti-CD4 antibody: Study in a murine model (2016)
  • Author(s): Norihiro Fujinami, Toshiaki Yoshikawa, Yu Sawada, Manami Shimomura, Tatsuaki Iwama, Shiori Sugai, Shigehisa Kitano, Yasushi Uemura, Tetsuya Nakatsura
  • Journal Title: Biochemistry and Biophysics Reports Volume: 5 Pages: 482-91
  • DOI: 10.1016/j.bbrep.2016.02.010
  • Peer Reviewed
• [Presentation] Cellular adjuvant properties and direct cytotoxicity in rejuvenated Vα24 invariant NKT cells from human induced pluripotent stem cells (2016)
  • Author(s): ZHANG Rong, KITAYAMA Syuichi, LIU Tianyi, UEDA Norihiro, IWAMA Tatsuaki, NAKATSURA Tetsuya, KUZUSHIMA Kiyotaka, KANEKO Shin, UEMURA Yasushi
  • Organizer: 第45回日本免疫学会学術総会
  • Place of Presentation: 沖縄コンベンションセンター・宜野湾市
  • Year and Date: 2016-12-05
• [Presentation] Therapeutic potential of dasatinib for acute graft versus leukemia disease (2016)
  • Author(s): 張 エイ, 上田 格弘, 喜多山 秀一, 安井 裕, 土屋 伸広, 劉 天懿, 岩間 達章, 葛島 清隆, 中面 哲也, 清井 仁 , 金子 新, 植村 靖史
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜・横浜市
  • Year and Date: 2016-10-06
• [Presentation] iPSC-pMCs genetically engineered to express IFNa as a potential cell medicine for cancer (2016)
  • Author(s): TSUCHIYA Nobuhiro, UEMURA Yasushi, IWAMA Tatsuaki, ZHANG Rong, SUZUKI Toshihiro, YOSHIKAWA Toshiaki, SAWADA Yu, TAKUBO Keiyo, SAKAGAMI-SAWANO Asako, MIYAWAKI Atsushi, ENDO Itaru, NAKATSURA Tetsuya
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜・横浜市
  • Year and Date: 2016-10-06
• [Presentation] インターフェロンαを産生するiPS細胞由来増殖性ミエロイド細胞を用いたがん免疫療法 (2016)
  • Author(s): 土屋 伸広, 植村 靖史, 岩間 達章, 張 エイ, 得光 友美, 鈴木 利宙, 吉川 聡明, 澤田 雄, 田久保 圭誉, 阪上-沢野 朝子, 宮脇 敦史, 遠藤 格, 中面 哲也
  • Organizer: 第20回日本がん免疫学会総会
  • Place of Presentation: 大阪カンファレンスセンター&ホテル・大阪市
  • Year and Date: 2016-07-27
• [Presentation] 活性化iNKT によるIL-12 ファミリーサイトカイン/オステオポンチンのバランス制御 (2015)
  • Author(s): 岩間達章、鈴木元晴、劉天懿、張エイ、吉川聡明、下村真菜美、中面哲也、葛島清隆、植村靖史
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋・名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] GPC3 由来ペプチド結合リポソームワクチン投与によりGPC3 発現がん細胞の成長を抑制する (2015)
  • Author(s): 土屋伸広、岩間達章、内田哲也、下村真菜美、吉川聡明、藤浪紀洋、齋藤友貴、植村靖史、中面哲也
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋・名古屋国際会議場
  • Year and Date: 2015-10-08