Combination of telomerase-specific oncolytic adenovirus and immune checkpoint inhibitor

• Project/Area Number: 16K19893
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Okayama University
• Principal Investigator: Kuroda Shinji 岡山大学, 大学病院, 助教 (60633758)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 腫瘍融解アデノウイルス / 抗PD-1抗体 / 免疫チェックポイント阻害剤 / 複合免疫療法 / 免疫原性細胞死 / ウイルス療法 / 免疫チェックポイント / 腫瘍浸潤リンパ球 / アブスコパル効果 / 免疫チェックポイント阻害 / 免疫療法

Outline of Final Research Achievements

Telomerase-specific oncolytic adenovirus facilitated CD8-positive cytotoxic T lymphocytes recruitment into tumor tissues through immunogenic cell death induction after intratumoral administration, leading to activation of systemic antitumor immune responses. Combination therapy with PD-1 Ab created synergistic antitumor effects that even led to tumor eradication. These findings support the contention that novel therapeutic strategies employing oncolytic virotherapy are ideal partners for immune checkpoint inhibitors and that this combination can yield improved clinical benefits for patients with advanced tumors with distant metastases.

Academic Significance and Societal Importance of the Research Achievements

新規治療法である腫瘍融解アデノウイルス療法は、強力に宿主の抗腫瘍免疫を活性化する治療法であり、抗腫瘍免疫のブレーキを解除することで治療効果を発揮する抗PD-1抗体などの免疫チェックポイント阻害剤との併用は理想的な治療戦略である。腫瘍に対するウイルスの局所治療が全身性の抗腫瘍免疫を活性化することから、遠隔転移部における抗腫瘍効果の増強にもつながり、さらなる治療成績の改善が期待される。

Research Products

• [Presentation] Telomelysin-induced immunogenic cell death synergizes with anti-PD-1 antibody in non-immunogenic gastrointestinal tumors (2018)
  • Author(s): Nobuhiko Kanaya, Shinji Kuroda, Toshiaki Morihiro, Yoshihiko Kakiuchi, Tetsushi Kubota, Satoru Kikuchi, Masahiko Nishizaki, Yasuo Urata, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara
  • Organizer: AACR 2018
  • Int'l Joint Research
• [Presentation] 腫瘍選択的融解アデノウイルス療法が腫瘍内リンパ球浸潤を増加させ，抗PD-1抗体の感受性を増強させる (2018)
  • Author(s): 金谷信彦，黒田新士，垣内慶彦，森廣俊昭，菊地覚次，田澤大，浦田泰生，西崎正彦，香川俊輔，藤原俊義
  • Organizer: 第39回癌免疫外科研究会
• [Presentation] テロメラーゼ活性依存的腫瘍融解アデノウイルスと抗PD-1抗体による新たな複合免疫療法の開発 (2018)
  • Author(s): 金谷信彦，黒田新士，垣内慶彦，森廣俊昭，菊地覚次，西崎正彦，浦田泰生，田澤大，香川俊輔， 藤原俊義
  • Organizer: 第73回日本消化器外科学会総会
• [Presentation] Immunogenic potential of Telomelysin sensitizing gastrointestinal tumors to anti-PD-1 antibody (2018)
  • Author(s): Nobuhiko Kanaya, Shinji Kuroda, Yoshihiko Kakiuchi, Toshiaki Morihiro, Tetsushi Kubota, Satoru Kikuchi, Masahiko Nishizaki, Yasuo Urata, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara
  • Organizer: 第24回日本遺伝子細胞治療学会学術集会
• [Presentation] Immunogenic Telomelysin synergizes with anti-PD-1 antibody in gastrointestinal tumors to anti-PD-1 antibody (2018)
  • Author(s): Nobuhiko Kanaya, Shinji Kuroda, Yoshihiko Kakiuchi, Toshiaki Morihiro, Tetsushi Kubota, Satoru Kikuchi, Masahiko Nishizaki, Yasuo Urata, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara
  • Organizer: 第22回日本がん免疫学会総会
• [Presentation] Telomelysin as an immunotherapy agent sensitizing gastrointestinal tumors to anti-PD-1 antibody (2018)
  • Author(s): Nobuhiko Kanaya, Shinji Kuroda, Kento Kumon, Yoshihiko Kakiuchi, Toshiaki Morihiro, Tetsushi Kubota, Hiroshi Tazawa, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Yasuo Urata, Toshiyoshi Fujiwara
  • Organizer: 第77回日本癌学会学術集会
• [Presentation] 腫瘍内リンパ球浸潤を誘導するテロメライシンと抗PD-1抗体を用いた新規複合免疫療法の開発 (2018)
  • Author(s): 金谷信彦，黒田新士，公文剣斗，垣内慶彦，森廣俊昭，菊地覚次，西崎正彦，浦田泰生，田澤大，香川俊輔，藤原俊義
  • Organizer: 第31回日本バイオセラピィ学会学術集会
• [Presentation] Combination of PD-L1 expression and microsatellite instability status is a useful and attractive prognostic factor in gastric cancer (2017)
  • Author(s): Toshiaki Morihiro, Shinji Kuroda, Nobuhiko Kanaya, Toshiyoshi Fujiwara, et al.
  • Organizer: AACR Anunal Meeting 2017
  • Place of Presentation: Washington DC
  • Year and Date: 2017-04-01
  • Int'l Joint Research
• [Presentation] Attractive ability of telomerase-specific oncolytic adenovirus as an immunogenic drug (2017)
  • Author(s): Nobuhiko Kanaya, Shinji Kuroda, Toshiaki Morihiro, Tetsushi Kubota, Hiroshi Tazawa, Satoru Kikuchi, Masahiko Nishizaki, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara
  • Organizer: 第23回日本遺伝子細胞治療学会
• [Presentation] Potential of telomerase-specific oncolytic adenovirus as an immunogenic drug producing synergy with anti-PD-1 therapy (2017)
  • Author(s): Nobuhiko Kanaya, Shinji Kuroda, Toshiaki Morihiro, Tetsushi Kubota, Hiroshi Tazawa, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Yasuo Urata, Toshiyoshi Fujiwara
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] テロメラーゼ依存的腫瘍選択的融解アデノウイルス製剤の免疫原性薬剤としての可能性と抗PD-1抗体との併用療法の有用性 (2017)
  • Author(s): 金谷信彦，黒田新士，垣内慶彦，森廣俊昭，久保田哲史，田澤大，菊地覚次，西崎正彦，香川俊輔，藤原俊義
  • Organizer: 第30回日本バイオセラピィ学会学術集会総会