Development of PD-1 gene-disrupted EGFRvIII-specific CAR-T cell-based immunotherapy against glioblastoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16567
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Nara Medical University
• Principal Investigator: Nakazawa Tsutomu 奈良県立医科大学, 医学部, 研究員 (00772500)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: CAR / PD-1 / CRISPR/Cas / EGFRvIII

Outline of Final Research Achievements

The present study showed that PD-1-disrupted EGFRvIII-specific CAR-T cells were established using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). The sgRNA/Cas9 expression vectors designed precisely disrupted the target region of PD-1 and inhibited the expression of PD-1 in EvCAR-T cells. The PD-1-disrupted EvCAR-T cells had an in vitro growth inhibitory effect on EGFRvIII-expressing glioblastoma cells without altering the T-cell phenotype and the expression of other checkpoint receptors.

Free Research Field

脳腫瘍学、免疫治療学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

将来的に、PD-1破壊EGFRvIII特異的CAR-T細胞のin vivoにおける抗がん効果解析や3次元培養系を用いた抗がん効果解析を実施し、膠芽腫に対する抗がん効果が認められれば、GBMに対するEGFRvIII特異的vCAR-T細胞を用いた膠芽腫に対するがん免疫治療の有効性を向上させることが可能と考えられる。