論文

査読有り 国際誌
2020年3月4日

Immune Modulation by Telomerase-Specific Oncolytic Adenovirus Synergistically Enhances Antitumor Efficacy with Anti-PD1 Antibody.

Molecular therapy
  • Nobuhiko Kanaya
  • Shinji Kuroda
  • Yoshihiko Kakiuchi
  • Kento Kumon
  • Tomoko Tsumura
  • Masashi Hashimoto
  • Toshiaki Morihiro
  • Tetsushi Kubota
  • Katsuyuki Aoyama
  • Satoru Kikuchi
  • Masahiko Nishizaki
  • Shunsuke Kagawa
  • Hiroshi Tazawa
  • Hiroyuki Mizuguchi
  • Yasuo Urata
  • Toshiyoshi Fujiwara
  • 全て表示

28
3
開始ページ
794
終了ページ
804
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ymthe.2020.01.003

The clinical benefit of monotherapy involving immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 antibody (PD-1 Ab) is limited to small populations. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), the safety of which was confirmed in a phase I clinical study. Here, we examined the potential of OBP-502, an OBP-301 variant, as an agent for inducing immunogenic cell death (ICD) and synergistically enhancing the efficacy of OBP-502 with PD-1 Ab using CT26 murine colon cancer and PAN02 murine pancreatic cancer cell lines. OBP-502 induced the release of ICD molecules such as adenosine triphosphate (ATP) and high-mobility group box protein 1 (HMGB1) from CT26 and PAN02 cells, leading to recruitment of CD8-positive lymphocytes and inhibition of Foxp3-positive lymphocyte infiltration into tumors. Combination therapy involving OBP-502 intratumoral administration and PD-1 Ab systemic administration significantly suppressed the growth of not only OBP-502-treated tumors but also tumors not treated with OBP-502 (so-called abscopal effect) in CT26 and PAN02 bilateral subcutaneous tumor models, in which active recruitment of CD8-positve lymphocytes was observed even in tumors not treated with OBP-502. This combined efficacy was similar to that observed in a CT26 rectal orthotopic tumor model involving liver metastases. In conclusion, telomerase-specific oncolytic adenoviruses are promising candidates for combined therapies with ICIs.

リンク情報
DOI
https://doi.org/10.1016/j.ymthe.2020.01.003
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31991110
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054725
ID情報
  • DOI : 10.1016/j.ymthe.2020.01.003
  • PubMed ID : 31991110
  • PubMed Central 記事ID : PMC7054725

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