Development of innovative combined cancer immunotherapy using immune checkpoint blockade for digestive cancers

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21359
• Project/Area Number (Other): 18H06267 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Fukuoka Dental College
• Principal Investigator: Okano Shinji 福岡歯科大学, 口腔歯学部, 准教授 (10380429)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 癌免疫療法 / 免疫チェックポイント阻害剤 / 癌集学的治療 / 癌抗原特異的T細胞 / 癌ゲノム不安定性

Outline of Final Research Achievements

It is important to obtain knowledge about interaction between immune checkpoint inhibitors (ICs) and current standard cancer treatments in combined cancer immunotherapy (CCI).We assessed mechanisms of antitumor effects in the CCI and basic principle for the administration timing of combined drugs using mouse colon adenocarcinoma models. The chemotherapy induced immunogenic cancer cell death and tumor-specific cytotoxic T lymphocytes (TC) responses, and dramatically increased numbers of IFN-gamma producing CD4 and CD8 T cells and TC within the tumors, suggesting that the administration order of the chemotherapy followed by the anti-PD-1 antibody was important (anti-PD-1 treatment was essential for in vivo anti-tumor effects by TC).Chemotherapy reduced not only tumor cell numbers, but also numbers of myeloid-derived suppressor cells and TC. Development of drugs to selectively induce cell death of specific target cells is a promising strategy for new CCIs.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

免疫原性癌細胞死から腫瘍抗原特異的T細胞誘導及び抗腫瘍効果に至る「殺細胞治療関連がん免疫サイクル」を考慮に入れた効率の良いがん複合免疫療法の投与レジメ検討の提唱と新規がん免疫複合療法の開発の一つの標的を提案することができ、がん患者の予後改善のために本研究分野の更なる推進と応用が期待されることを示すことができた。