Development of preclinical models of donor-derived gene-modified lymphocyte infusion for tumor-relapse after allogeneic hematopoietic cell transplantation and evaluation of efficacy and safety

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09949
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Mie University
• Principal Investigator: TAWARA Isao 三重大学, 医学部附属病院, 講師 (80378380)
• Co-Investigator(Kenkyū-buntansha): 池田 裕明 長崎大学, 医歯薬学総合研究科(医学系), 教授 (40374673)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 造血細胞移植 / 移植後腫瘍再発 / ドナーリンパ球輸注 / 腫瘍特異的リンパ球 / 移植片対宿主病

Outline of Final Research Achievements

We generated murine models of tumor relapse after major histocompatibility complex (MHC)-matched or mismatched allogeneic hematopoietic cell transplantation (HCT) and performed tumor-specific donor lymphocyte infusion (DLI) 2 or 8 weeks after HCT. Anti-tumor effect was observed in each setting and GVHD was aggravated graft-vs-host disease (GVHD) in the animals when we performed tumor-specific DLI 2 weeks after HCT. GVHD aggravation was observed only in the recipients of MHC-matched HCT, not in those of MHC-mismatched HCT when we performed tumor-specific DLI 8 weeks after HCT. Our pre-clinical data suggest that GVHD aggravation caused by tumor-specific DLI is dependent on timing and MHC disparity. This study will contribute to clinical development of tumor-specific DLI for the tumor-relapsed patients after allogeneic HCT.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、同種造血細胞移植における臨床的課題である移植後腫瘍再発に対して、腫瘍特異的遺伝子改変ドナーリンパ球輸注療法（DLI）を実施することを念頭においた、前臨床研究である。研究成果は、腫瘍特異的DLIを実施する際に懸念されるGVHDへの影響が、レシピエントの状態、MHC適合度によって異なること示しており、より効果的で安全な腫瘍特異的DLIの臨床開発において、重要な基礎データになると考えられる。