Development of combination therapy of cytokine signaling suppressor virus and anti-PD-L1 antibody

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16907
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Nagoya University
• Principal Investigator: Ichinose Toru 名古屋大学, 医学系研究科, 研究員 (60778091)
• Research Collaborator: KASUYA hideki ; NAOE yoshinori ; MATSUMURA shigeru ; BUSTOS itzel ; EISSA ibrahim
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 腫瘍溶解性ウイルス / 癌 / サイトカインシグナル / 免疫チェックポイント / 頭頸部がん

Outline of Final Research Achievements

The purpose of this study was to develop new treatments by combining oncolytic virus HF10 that was genetically modified to express the inhibitory regulator SOCS1 of the Jak / Stat pathway in the viral genome and the immune checkpoint inhibitor to improve treatment outcome for head and neck cancer. A foreign gene cassette vector was constructed, and we succeeded in creating HF10-SOCS1 into which the regulatory SOCS1 gene was integrated by homologous recombination with the HF10 genome. We examined the combined effect of HF10-SOCS1 and immune checkpoint inhibitors on bilateral flank tumors of mouse squamous cell carcinoma SCC7 cell line and showed a stronger antitumor effect than HF10 on both tumors.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

本研究では、HF10-SOCS1 の感染と免疫チェックポイント阻害剤の投与により癌免疫抑制環境が改善され、癌抗原特異的T 細胞が腫瘍に強く浸潤し、体内のT細胞の機能も長く維持される事が期待される。本研究によって得られた結果はウイルス療法の新たな展開だけでなく、免疫細胞療法分野にも新しい知見を提供し、外科的切除のみでは治癒不可能な多くの癌患者さんの生命予後に寄与する可能性がある。