A novel cell thrapy using allogeneic CCL19-expressing mesenchymal stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15592
• 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: Shimane University
• Principal Investigator: Iida Yuichi 島根大学, 学術研究院医学・看護学系, 助教 (50734985)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 細胞医薬 / CCL19 / 間葉系幹細胞 / 樹状細胞

Outline of Final Research Achievements

We previously reported that local injection of syngeneic iMSC/CCL19 can suppress the tumor growth by promoting infiltration of T cells and CD45+ F4/80- CD11c+ CCR7+ cells (Iida et al., J of ImmunoTher Cancer 2020). To expand this strategy, we determined whether allogeneic iMSC/CCL19 could suppress the tumor growth. We founded that iMSC/CCL19 remained longer than iFib/CCL19. In therapeutic models using CT26, RENCA-OVA and B16-OVA-bearing mice, local injection of Allo-iMSC/CCL19 exerted drastic anti-tumor effect but not RENCA-bearing mice. Quantitative RT-PCR revealed that Allo-iMSC/CCL19 upregulated relative mRNA expression of p35, p40, CD11c, CD4, CD8, IFNγ and granzyme B. Since anti-asialoGM1 antibody and anti-IL12p40 antibody attenuated the anti-tumor effect of Allo-iMSC/CCL19, innate immune response are important. These results suggest that Allo-iMSC/CCL19 stimulated allo-reactive innate immune response not only T cells.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

我々は、効率よく抗原提示細胞やT細胞を腫瘍に集積させ、免疫チェックポイント阻害療法の奏効率を改善する新規細胞治療法(MSC/CCL19局所投与)をマウスモデルで確立してきた。自家移植では、時間と費用が必要であるため、本研究では他家移植を目指した非自己(アロ)MSC/CCL19による腫瘍抑制効果の検討およびメカニズムの解明を行った。アロMSC/CCL19は高い抗腫瘍効果を示し、抗がん応答メカニズムの一部が明らかとなった。アロMSC/CCL19の抗がん治療への応用は新規がん免疫療法となる可能性を秘めている。