Development of methods controlling infused lymphocytes based on the immunopathology of acute GVHD and cytokine release syndrome.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Mie University
• Principal Investigator: Tawara Isao 三重大学, 医学系研究科, 教授 (80378380)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 同種造血幹細胞移植 / 特異的リンパ球輸注療法 / 移植片対宿主病

Outline of Final Research Achievements

To develop of methods controlling infused lymphocytes based on the immunopathology of acute GVHD and cytokine release syndrome, we generated mouse models of allogeneic bone marrow transplantation, tumor-specific gene-modified lymphocyte infusion into non-transplant (syngeneic) tumor-bearers or allogeneic transplant tumor-bearers.
In the allogeneic bone marrow transplantation model, mice developed acute GVHD and infiltrated donor cells could be detected in the intestinal tract. Insufficient anti-tumor effect was observed in the model of tumor-specific lymphocyte infusion into non-transplant mice. GVHD exacerbation along with tumor regression were observed in the model of tumor-specific lymphocyte infusion into post-allogeneic transplant mice. The onset of anti-tumor effect was thought to be influenced by the time from tumor challenge to specific lymphocyte infusion.

Free Research Field

血液・腫瘍内科学

Academic Significance and Societal Importance of the Research Achievements

抗腫瘍効果が輸注リンパ球によって発揮される同種造血幹細胞移植や、腫瘍特異的遺伝子改変リンパ球輸注療法では、急性GVHDやサイトカイン放出症候群といった合併症が起こる。その詳細なメカニズムは不明であり、輸注リンパ球の制御法の開発は臨床的課題である。今後、これらの領域では細胞源（ソース）や改変（導入）遺伝子の多様化が考えられ、合併症への対応は引き続き重要な課題である。
現時点では十分な結果が得られたとは言い難いが、本研究を継続することで、輸注リンパ球が引き起こす合併症のメカニズムが明らかとなり、科学的根拠に基づいた輸注リンパ球制御法の開発が期待される。