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2020 Fiscal Year Final Research Report

Development of genetically modified iPS cell derived M1 macrophage therapy against melanoma

Research Project

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Project/Area Number 18K08301
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionKumamoto University

Principal Investigator

FUKUSHIMA SATOSHI  熊本大学, 大学院生命科学研究部(医), 教授 (50398210)

Co-Investigator(Kenkyū-buntansha) 尹 浩信  熊本大学, 大学院生命科学研究部(医), 教授 (20282634)
Project Period (FY) 2018-04-01 – 2021-03-31
Keywordsメラノーマ / iPS細胞 / マクロファージ / がん免疫療法 / 腫瘍微小環境 / 免疫細胞療法 / サイトカイン / 免疫チェックポイント分子
Outline of Final Research Achievements

We reported the efficacy of an immune cell therapy with immortalized myeloid cells derived from induced pluripotent stem cells (iPS-ML). We generated OX40L-overexpressing iPS-MP (iPS-MP-OX40L) and investigated their characteristics and in vivo efficacy against mouse melanoma. We found that iPS-ML-Zsgreen-OX40L suppressed the progression of B16-BL6 melanoma, and prolonged survival of mice with ovalbumin (OVA)-expressing B16 melanoma (MO4). The number of antigen-specific CD8+ T cells
was higher in spleen cells treated with OVA peptide-pulsed iPS-MP-OX40L than in those without OX40L. The OVA peptide-pulsed iPS-MP-OX40L significantly increased the number of tumor-infiltrating T lymphocytes in MO4 tumor. Flow cytometry showed decreased regulatory T cells but increased effector
and effector memory T cells among the TILs.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

近年、がん免疫療法の有効性が明らかとなっていが、その有効率は未だ十分ではない。どうやったら現在の免疫療法が無効な患者に対して、有効な治療法を確立することができるか、その答えのひとつとして、iPS細胞を用いた遺伝子改変免疫細胞療法を提案する。免疫を活性化する分子を発現させたiPS細胞由来マクロファージはマウスモデルで強い効果を示した。またその安全性も確認した。

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Published: 2022-01-27  

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