Cancer immunotherapy by combining the selective COX-2 inhibitor and type I IFN signaling

• Project/Area Number: 16K19071
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Asahikawa Medical College
• Principal Investigator: KOSAKA Akemi 旭川医科大学, 医学部, 助教 (40561030)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: COX-2阻害薬 / STINGアゴニスト / 抗腫瘍効果 / 抗腫瘍免疫 / 腫瘍免疫 / がん免疫療法

Outline of Final Research Achievements

The aim for this study is to development of an efficient and convenient cancer immunotherapy and to elucidate the mechanism when combining the selective COX-2 inhibitor celecoxib and the type I IFN inducer 2’3’-cGAMP.We used different mouse tumor models to determine the treatment regimen of celecoxib and 2’3’-cGAMP. The combination therapy showed a significant antitumor effect on tumor growth in mice compared to control and monotherapy with celecoxib or 2’3’-cGAMP. The antitumor effect of the combination therapy was not dependent on CD8+ T-cells and macrophages, and it was suggested that the type I IFN signaling pathway may not be involved in the antitumor responses of the combination therapy.

Research Products

• [Journal Article] Intratumoral administration of cGAMP transiently accumulates potent macrophages for anti-tumor immunity at a mouse tumor site. (2017)
  • Author(s): Ohkuri T, Kosaka A, Ishibashi K, Kumai T, Hirata Y, Ohara K, Nagato T, Oikawa K, Aoki N, Harabuchi Y, Celis E, Kobayashi H.
  • Journal Title: Cancer Immunology, Immunotherapy Volume: - Issue: 6 Pages: 705-716
  • DOI: 10.1007/s00262-017-1975-1
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant