Development of innovative combination therapy of tumor antigen virus and TCR gene-modified T cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15611
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Nagoya University
• Principal Investigator: KASUYA Hideki 名古屋大学, 医学系研究科, 教授 (00402636)
• Co-Investigator(Kenkyū-buntansha): 駱 晨虹 名古屋大学, 医学系研究科, 招へい教員 (40759627)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: HF10 / 癌 / 免疫細胞療法 / 癌抗原

Outline of Final Research Achievements

In this study, we investigated the possibility of novel therapeutic approach for cancer based on the combination of transgenic HF10, the oncolytic herpes simplex virus that genetically modified to express cancer-specific antigen, and TCR gene-modified T cells recognizing cancer antigen produced from transgenic HF10. We steadily advanced the preparation of research by establishing the cancer antigen-expressing cells and confirming the cell-killing effect of T cells. We examined the usefulness of novel genomic editing technology for homologous recombination efficiency, and found that novel genomic editing is a very suitable technique for improvement of homologous recombination and purification of genetically modified virus. In the future, we will advance the development of cancer antigen gene-carrying HF10 using this technology, accumulate basic data on combination therapy with antigen specific TCR gene-modified T cells, and explore the possibility of clinical application.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

腫瘍溶解性ウイルス療法は感染を拡大させながら大量の癌細胞を殺傷し、腫瘍抗原に対する免疫抑制環境を改善することにより、腫瘍抗原特異的な免疫を誘導する。その後の抗腫瘍効果はIn situ Vaccinationとしての抗腫瘍特異的免疫によると考えている。抗腫瘍免疫反応を高めるため、我々は腫瘍抗原遺伝子をHF10に導入し、ウイルスに導入した腫瘍抗原が通常含有量よりも大量に腫瘍内に発現する事を利用して、腫瘍抗原に対してウイルス抗原と同じ強い免疫反応を引き起こし、MUC-HF10によって免疫抑制環境が改善する事と相まって遺伝子改変T細胞療法のターゲットへの精確性、効率性を高める点に新たな着想がある。