Combining oncolytic virus with genetically modified T cell therapy for the treatment of cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15702
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Shinshu University
• Principal Investigator: Saito Shoji 信州大学, 学術研究院医学系(医学部附属病院), 講師 (10623762)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: がん免疫療法

Outline of Final Research Achievements

We sought to optimize the generation method of X-antigen specific CAR-T cells. By modifying the types of feeder cells and the schedule of stimulation and cytokine supplementation, we successfully improved the efficiency of CAR-T generation. The generated CAR-T cells exhibited a naive / stem cell memory-like phenotype and minimally expressed T cell exhaustion markers, such as PD1. We have switched the oncolytic viruses to nanoparticle to deliver target genes to tumor cells for future clinical applications. We have developed a novel nanoparticle that can selectively enter tumor cells but not normal peripheral blood mononuclear cells (PBMCs). When these nanoparticles were loaded with firefly luciferase(ffLuc) mRNA, they could efficiently deliver mRNA to the tumor cells, with enhanced luciferase activity, but they minimally delivered ffLuc mRNA to PBMCs. Now, we are further investigating these nanoparticles to deliver target mRNA to modify tumor cells to express X antigen.

Free Research Field

小児血液がん

Academic Significance and Societal Importance of the Research Achievements

PiggyBac法を用いたCAR-T細胞の培養法については顕著な改良が得られ、改良型CAR-T細胞単独もしくは腫瘍溶解ウイルス療法を組み合わせることで、難治性がんに対する革新的な治療法開発につながることが期待される。また、本研究では、腫瘍溶解ウイルスに代わる全く新しい腫瘍細胞遺伝子改変の技術を開発した。本研究で開発した腫瘍選択性ナノ粒子を用いて、腫瘍に選択的に治療遺伝子を導入する治療戦略は、単独もしくはCAR-T療法との併用により、がんに対する革新的な治療法開発につながることが期待される。