Development of a co-stimulator-expressing oncolytic virus that contributes to the improvement of " immunological exhaustion" of CAR-T cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23894
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yoshida HIdeki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10643546)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 腫瘍溶解性アデノウイルス / 横紋筋肉腫 / CAR-T細胞療法 / 免疫学的疲弊 / 共刺激因子

Outline of Final Research Achievements

1) We made an RMS cell line (Rh30) expressing the co-stimulator CD80 using an expression vector pcDNA3.1(+). We also confirmed that the expression was stable by flow cytometry. 2) CD80-expressing Rh30 and wild-type Rh30, and CAR-T were co-cultured respectively, and then the antitumor effect on Rh30 was evaluated by a real time analyzer. The cell number of CD80-expressing Rh30 was suppressed for a long time by CAR-T. This result suggests a reduction in immunological exhaustion. 3) Based on the MYOG promoter-controlled OAd, a viral plasmid in which the E1 gene, T2A, and CD80 were linked was prepared. We are currently verifying whether it can be assembled as a virus.

Free Research Field

小児悪性疾患腫瘍

Academic Significance and Societal Importance of the Research Achievements

がん患者の腫瘍免疫機構を回復させるために、細胞傷害性T細胞（CTL）がもつT細胞受容体（TCR）に対して遺伝子改変したCAR-T細胞を用いたがん治療は、すでに一部の急性リンパ性白血病や悪性リンパ腫に対して使用されているが、血液腫瘍以外の小児固形腫瘍のCAR-T細胞療法はいまだ研究レベルの域を出ていない。標的となるがん細胞上に共刺激因子を発現させる遺伝子改変OAdをCAR-Tと併用することで、T細胞に生じる『免疫学的疲弊』を軽減し、抗腫瘍効果を増強させることができれば、固形腫瘍に対するCAR-T細胞療法の治療効果を著しく高める可能性がある。