Combined anti-cancer immunotherapy based on the ability of immune responses in aged hosts

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07217
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Shimane University
• Principal Investigator: Harada Mamoru 島根大学, 学術研究院医学・看護学系, 教授 (50260716)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 免疫療法 / 加齢 / 化学療法 / 集学的がん治療

Outline of Final Research Achievements

The in vivo growth of murine colon carcinoma CT26 was more rapid in aged mice compared to young mice, and the serum levels of IL-6 were elevated in aged mice. In addition, aged mice showed lower response to anti-cancer vaccine by inactivated cancer cells compared to young mice. On the other hand, we examined the immune responses to murine renal carcinoma RENCA expressing human CA9 (hCA9) as a non-self antigen. As a result, young mice rejected RENCA/hCA9 and human CA9-recognizing CD8+ T cells and CD4+ T cells were induced in such mice. In addition, aged mice allowed RENCA/hCA9 to grow in vivo but combined immunotherapy with immune checkpoint blockade therapy with chemotherapy exerted significant antitumor effects even in aged mice.

Free Research Field

がん免疫療法

Academic Significance and Societal Importance of the Research Achievements

本研究では、加齢担がん生体での有効な複合免疫療法の確立を目指した。加齢に伴い炎症性サイトカインが上昇し、担がん状態の場合さらに炎症状態が悪化する。また、加齢担がん生体では強力な化学療法を受けた後では骨髄抑制が生じ、抗がんT細胞を再賦活させる免疫チェックポイント抗体療法も効果を示さないかもしれない。研究の成果は、実臨床において、がん患者の大部分を占める中高年のがん患者に対して複合免疫療法を実施する場合の貴重な基盤的情報になり、高齢化が進む本邦における複合抗がん免疫療法の適応拡大に大いに貢献できると予想される。