Biological effects of prostaglandin E2-EP4 antagonist (AAT-008) in murine colon cancer in vivo: enhancement of immune response to radiotherapy and potential as a radiosensitizer

• Project/Area Number: 18K15285
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nagoya City University
• Principal Investigator: Manabe Yoshihiko 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (00769838)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 免疫賦活化放射線治療 / 放射線増感剤 / 抗腫瘍免疫 / 放射線増感効果 / 免疫治療 / 放射線治療

Outline of Final Research Achievements

AAT-008 potentially enhances the radiosensitivity of colon cancer cells, apparently by stimulating the immune system against the cancer cells.

Academic Significance and Societal Importance of the Research Achievements

放射線治療には放射線そのものによる腫瘍へのダメージと、抗腫瘍免疫活性化による効果が期待される。AAT-008は放射線治療と併用することで抗腫瘍免疫をさらに活性化させることが示唆された。この薬剤は人体への投与を前提に作成されているため実臨床応用しやすい利点がある。現在臨床で使用されている化学療法・分子標的薬・免疫チェックポイント阻害薬に加えて、新たな選択肢となる可能性がある。

Research Products

• [Journal Article] Biological effects of prostaglandin E2-EP4 antagonist (AAT-008) in murine colon cancer in vivo: enhancement of immune response to radiotherapy and potential as a radiosensitizer (2023)
  • Author(s): Manabe Y, Takahashi Y, Sugie C, Wang Z, Katsuki S, Kondo T, Murai T, Nakashima M, Takaoka T, Ogawa K, Shibamoto Y
  • Journal Title: Transl Cancer Res Volume: 12(2) Issue: 2 Pages: 351-358
  • DOI: 10.21037/tcr-22-1857
  • Peer Reviewed / Open Access
• [Journal Article] Stereotactic body radiotherapy using a hydrogel spacer for localized prostate cancer: A dosimetric comparison between tomotherapy with the newly‐developed tumor‐tracking system and cyberknife (2021)
  • Author(s): Manabe Yoshihiko、Hashimoto Seiji、Mukouyama Hideki、Shibamoto Yuta
  • Journal Title: Journal of Applied Clinical Medical Physics Volume: 22 Issue: 10 Pages: 66-72
  • DOI: 10.1002/acm2.13395
  • Peer Reviewed / Open Access
• [Journal Article] Stereotactic body radiotherapy using the forward-planned static-port tomotherapy for lung cancer: a novel planning technique with the newly-developed mode (2020)
  • Author(s): Manabe Yoshihiko、Miyakawa Akifumi、Kondo Takuhito、Yamada Yuki、Hashimoto Seiji、Ishikura Satoshi、Shibamoto Yuta
  • Journal Title: Journal of Radiation Research Volume: 61 Issue: 6 Pages: 993-998
  • DOI: 10.1093/jrr/rraa092
  • Peer Reviewed / Open Access
• [Journal Article] Intensity-modulated radiation therapy for multiple targets with tomotherapy using multiple sets of static ports from different angles (2020)
  • Author(s): Manabe Yoshihiko、Shibamoto Yuta、Murai Taro、Torii Akira、Niwa Masanari、Kondo Takuhito、Okazaki Dai、Sugie Chikao
  • Journal Title: Journal of Applied Clinical Medical Physics Volume: - Issue: 6 Pages: 132-138
  • DOI: 10.1002/acm2.12874
  • Peer Reviewed / Open Access
• [Journal Article] Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy (2020)
  • Author(s): Tomita Natsuo、Uchiyama Kaoru、Mizuno Tomoki、Imai Mikiko、Sugie Chikao、Ayakawa Shiho、Niwa Masanari、Matsui Tooru、Otsuka Shinya、Manabe Yoshihiko、Nomura Kento、Kondo Takuhito、Kosaki Katsura、Miyakawa Akifumi、Miyamoto Akihiko、Takemoto Shinya、Kitagawa Yuto、Yasui Takahiro、Shibamoto Yuta
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 114-114
  • DOI: 10.1038/s41598-019-57056-9
  • Peer Reviewed / Open Access
• [Journal Article] Significant reduction of oncologic pulmonary death by local control for pulmonary oligometastases treated with stereotactic body radiotherapy (2020)
  • Author(s): Yamamoto Takaya、Niibe Yuzuru、Yamada Kazunari、Aoki Masahiko、Onishi Hiroshi、Katsui Kuniaki、Dekura Yasuhiro、Nishikawa Atsushi、Manabe Yoshihiko、Yamashita Hideomi、Jingu Keiichi
  • Journal Title: Radiotherapy and Oncology Volume: 147 Pages: 86-91
  • DOI: 10.1016/j.radonc.2020.03.019
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of herbal medicine TJ-14 for acute radiation-induced enteritis: a multi-institutional prospective Phase II trial (2019)
  • Author(s): Murai Taro、Matsuo Masayuki、Tanaka Hidekazu、Manabe Yoshihiko、Takaoka Taiki、Hachiya Kae、Yamaguchi Takahiro、Otsuka Shinya、Shibamoto Yuta
  • Journal Title: Journal of Radiation Research Volume: 61 Issue: 1 Pages: 140-145
  • DOI: 10.1093/jrr/rrz025
  • Peer Reviewed / Open Access
• [Journal Article] Helical tomotherapy for chemo‐refractory multiple liver metastases (2019)
  • Author(s): Takaoka Taiki、Shibamoto Yuta、Murai Taro、Kobayashi Masanori、Sugie Chikao、Manabe Yoshihiko、Kondo Takuhito、Okazaki Dai、Yamada Yuki、Torii Akira
  • Journal Title: Cancer Medicine Volume: 8 Issue: 18 Pages: 7594-7602
  • DOI: 10.1002/cam4.2651
  • Peer Reviewed / Open Access
• [Journal Article] Pulmonary Oligometastases Treated by Stereotactic Body Radiation Therapy: A Nationwide Survey of 1,378 Patients (2019)
  • Author(s): NIIBE YUZURU、MANABE YOSHIHIKO(13番目)、他21名.
  • Journal Title: Anticancer Research Volume: 40 Issue: 1 Pages: 393-399
  • DOI: 10.21873/anticanres.13965
  • Peer Reviewed
• [Journal Article] Radiation-induced dermatitis after administration of mogamulizumab for adult T-cell leukaemia/lymphoma: a multi-institutional retrospective study. (2019)
  • Author(s): Maemoto H, Ariga T, Kusada T, Heianna J, Manabe Y, Miyakawa A, Nakachi S, Morishima S, Iraha S, Ganaha F, Masuzaki H, Murayama S
  • Journal Title: Jpn J Clin Oncol. Volume: 49 Issue: 2 Pages: 153-159
  • DOI: 10.1093/jjco/hyy172
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Evaluation of Onrad, A New Low-cost Version of TomoTherapy that Uses Only Static Beams (2018)
  • Author(s): MURAI TARO、TAMURA TAKESHI、NAKABAYASHI TADASHI、ITO HIROYA、MANABE YOSHIHIKO、MURATA RUMI、NIWA MASANARI、SHIBAMOTO YUTA
  • Journal Title: The Kurume Medical Journal Volume: 65 Issue: 4 Pages: 129-136
  • DOI: 10.2739/kurumemedj.MS654004
  • NAID: 130007789169
  • ISSN: 0023-5679, 1881-2090
  • Year and Date: 2018-12-31
  • Peer Reviewed / Open Access
• [Journal Article] Definitive radiotherapy for hilar and/or mediastinal lymph node metastases after stereotactic body radiotherapy or surgery for stage I non-small cell lung cancer: 5-year results (2018)
  • Author(s): Manabe Yoshihiko、Shibamoto Yuta、Baba Fumiya、Yanagi Takeshi、Iwata Hiromitsu、Miyakawa Akifumi、Murai Taro、Okuda Katsuhiro
  • Journal Title: Japanese Journal of Radiology Volume: 36 Issue: 12 Pages: 719-725
  • DOI: 10.1007/s11604-018-0776-6
  • NAID: 50013109623
  • Peer Reviewed / Open Access
• [Journal Article] Biological Effects of Continuous Low-Dose-Rate Irradiation in Silkworms and Mice: Growth Promotion and Tumor Transplantability. (2018)
  • Author(s): Nakashima M, Sugie C, Wang Z, Kondo T1, Manabe Y, Murai T, Shibamoto Y.
  • Journal Title: Dose Response Volume: 16(4) Issue: 4 Pages: 15593258-15593258
  • DOI: 10.1177/1559325818811753
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-term results of intensity-modulated radiotherapy with three dose-fractionation regimens for localized prostate cancer (2018)
  • Author(s): Takemoto Shinya、Shibamoto Yuta、Sugie Chikao、Manabe Yoshihiko、Yanagi Takeshi、Iwata Hiromitsu、Murai Taro、Ishikura Satoshi
  • Journal Title: Journal of Radiation Research Volume: 60 Issue: 2 Pages: 221-227
  • DOI: 10.1093/jrr/rry089
  • Peer Reviewed / Open Access
• [Journal Article] Differentiation between malignant and benign musculoskeletal tumors using diffusion kurtosis imaging (2018)
  • Author(s): Ogawa Masaki、Kan Hirohito、Arai Nobuyuki、Murai Taro、Manabe Yoshihiko、Sawada Yusuke、Shibamoto Yuta
  • Journal Title: Skeletal Radiology Volume: 48 Issue: 2 Pages: 285-292
  • DOI: 10.1007/s00256-018-2946-0
  • Peer Reviewed / Open Access
• [Presentation] PGE2-EP4受容体拮抗薬AAT-008による放射線増感効果 (2023)
  • Author(s): 眞鍋良彦、高橋 豊、杉江愛生、王 禎、勝木翔平、近藤拓人、村井太郎、中島雅大、高岡大樹、小川和彦、芝本雄太
  • Organizer: 第１９６回 日本医学放射線学会九州地方会
• [Presentation] PGE2-EP4受容体拮抗薬AAT-008による放射線増感効果 (2022)
  • Author(s): 眞鍋良彦、高橋 豊、杉江愛生、王 禎、勝木翔平、近藤拓人、村井太郎、中島雅大、高岡大樹、小川和彦、芝本雄太
  • Organizer: 第17回中部放射線治療研究会
• [Presentation] Biological effects of prostagrandin E2-EP4 antagonist (AAT-008): enhancement of immunoresponse to radiotherapy and a potential as a radiosensitizer (2021)
  • Author(s): Yoshihiko Manabe, Yutaka Takahashi, Chikao Sugie, Zhen Wang, Taro Murai, Masahiro Nakashima, Kazuhiko Ogawa, Yuta Shibamoto
  • Organizer: ASTRO 2021 annual meeting
  • Int'l Joint Research
• [Presentation] Stereotactic body radiotherapy using the newly-developed forward-planned static-port tomotherapy for lung cancer (2019)
  • Author(s): Yoshihiko Manabe, Akifumi Miyakawa, Takuhito Kondo, Yuki Yamada, Seiji Hashimoto, Yuta Shibamoto
  • Organizer: ASTRO 61th Annual Meeting
  • Int'l Joint Research
• [Presentation] Biological effects of prostagrandin E2-EP4 antagonist (AAT-008) : enhancement of immunoresponse to radiotherapy and a potential as a radiosensitizer (2019)
  • Author(s): Manabe Y, Takahashi T, Sugie C, Wang Z, Murai T, Nakashima M, Okumura T, Ogawa K, Shibamoto Y
  • Organizer: International Society of Radiation Neurobiology 9th meeting
  • Int'l Joint Research
• [Presentation] Intensity modulated radiation therapy for multiple targets with a static-port tomotherapy using a pseudo dynamic-jaw and dynamic-couch technique (2018)
  • Author(s): Manabe Y, Shibamoto S, Torii A, Niwa M, Kondo T, Okazaki D, Murai T, Sugie C
  • Organizer: American Society for Radiation Oncology 2018 Annual meeting
  • Int'l Joint Research