2013 Fiscal Year Final Research Report
Development of immunosuppressive microenvironment-breaking immune therapy with autologous hematopoietic stem cell transplantation
| Project/Area Number |
23590384
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
AOKI Kazunori 独立行政法人国立がん研究センター, 研究所, 分野長 (60270675)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 免疫抑制環境 / 制御性Ｔ細胞 / 造血幹細胞移植 / 低酸素 / 遺伝子導入 / プロモーター |
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| Research Abstract |
We have reported that autologous hematopoietic stem cell transplantation (HSCT) leads to an induction of antitumor immunity. However, many solid cancers are resistant to immune therapies, because they establish the immunosuppressive microenvironment in tumors. The regulatory T cells (Tregs) is a main factor of tumoral immunosuppression. On the other hand, the systemic depletion of Tregs may induce autoimmune reaction. Here, we developed a novel immune therapy with the genetic engineering of hematopoietic stem cells, which fundamentally break the immunosuppressive microenvironment in tumors. To eradicate Tregs in tumors only, we first analyzed the dynamics of Tregs in tumors after HSCT, and based the findings, we successfully developed a hypoxia-inducible Treg-specific transgene expression system, which is a basis of novel immune therapy.
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[Journal Article] In vivo interferon-αgene transfer enhances antitumor immunity afterautologous hematopoietic stem cell transplantation2012
Author(s)
Narumi K, Udagawa T, Kobayashi A, Hara H, Kondoh A, Goto N, Ikarashi Y, Ohnami S, Takeshita F, Ochiya T, Okada T, Yamagishi M, Yoshida T, Aoki K
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Journal Title
Gene Ther
Volume: 19
Pages: 34-48
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