PD-L1 as target for the development of a new oncolytic virus

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15274
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nagoya University
• Principal Investigator: Bustos Itzel 名古屋大学, 国際機構(医), 特任講師 (60788777)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 腫瘍溶解性ウイルス / 免疫チェックポイント / PD-L1 / 癌免疫

Outline of Final Research Achievements

The purpose of this study was to develop a novel oncolytic virus that not only has a tropism for PD-L1-expressing cells but also has a function as an immune checkpoint inhibitor. We have succeeded in constructing the anti-PD-L1 antibody gene vector, but have not yet created the desired virus. The combination of HF10 and anti-PD-L1 antibody against the bilateral flank tumors of mouse squamous cell carcinoma SCC VII showed a strong antitumor effect on the bilateral tumors. It was suggested that the infiltration of immune cells into the tumor is involved in this enhancement of antitumor effect.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

腫瘍への免疫細胞の浸潤について検討した結果、HF10単独ならびに抗PD-L1抗体との併用群でT細胞、マクロファージ、NK細胞、樹状細胞の浸潤が高率に認められ、これら免疫細胞の腫瘍への浸潤が併用効果の増強に関与することが考えられる。この結果はHF10αPD-L1の強い抗腫瘍効果を期待させる。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