Development of treatment strategy for chronic active EBV infection to eradicate EBV-infected tumor cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15578
• 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: St. Marianna University School of Medicine
• Principal Investigator: UCHIDA AKIKO 聖マリアンナ医科大学, 医学部, 講師 (70866889)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: EBウイルス

Outline of Final Research Achievements

Expression of BCL2 was confirmed in EBV-positive T/NK cell lines and peripheral blood mononuclear cells (PBMCs) derived from patients with CAEBV. The BCL2 inhibitor Venetoclax suppressed cell proliferation and the production of inflammatory cytokines in PBMCs from CAEBV patients. Furthermore, administration of Venetoclax to a CAEBV mouse model inhibited the infiltration of tumor cells infected with BV into the liver and spleen. Additionally, a tendency for decreased IFN-g levels in peripheral blood was observed in mice treated with Venetoclax. These results suggest that Venetoclax has the potential to suppress the primary symptoms of CAEBV and could be a promising new therapeutic agent.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

EBVは世界中のほぼすべてのヒトが感染している。なぜその一部でEBVがT,NK細胞への持続感染とクローナルな増殖を来してCAEBVを発症するのか、その機序は未解明である。また根治薬は未だ開発されていない。CAEBVは炎症症状で発症し、進行すると難治性リンパ腫へと進行して致死的経過をとる。本研究の結果はCAEBVの炎症症状のみならず、感染細胞自身の駆逐にも寄与し得る。CAEBVの報告はこれまで本邦に集中してきたが世界的に増えている。グローバルな患者の予後の改善に寄与し得る。