- 专利标题: USE OF MAIT CELLS FOR CONTROLLING GRAFT VERSUS HOST DISEASE
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申请号: US18256788申请日: 2021-12-09
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公开(公告)号: US20240075063A1公开(公告)日: 2024-03-07
- 发明人: Sophie CAILLAT-ZUCMAN , Nana TALVARD-BALLAND
- 申请人: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) , UNIVERSITE DE PARIS , ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS
- 申请人地址: FR Paris
- 专利权人: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE),UNIVERSITE DE PARIS,ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS
- 当前专利权人: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE),UNIVERSITE DE PARIS,ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS
- 当前专利权人地址: FR Paris
- 优先权: EP 306528.9 2020.12.10
- 国际申请: PCT/EP2021/085062 2021.12.09
- 进入国家日期: 2023-06-09
- 主分类号: A61K35/17
- IPC分类号: A61K35/17 ; A61P35/02
摘要:
The inventors explored in an allogeneic situation the regulatory potential of Mucosal-Associated Invariant T cells (MAIT cells), a population of unconventional T cells that exhibit potent antibacterial activity, expressing a semi-invariant TCR which recognizes vitamin B2 derivatives of microbial origin presented by the MR1 molecule. In particular, the inventors used i) an allogenic reaction model in vitro (mixed lymphocyte reaction, MLR) and ii) murine model of xenogeneic aGvHD They first verified that human MAIT cells do not proliferate in response to allogeneic stimulation in vitro (MLR) or in vivo (immunodeficient mice) alone but require for their expansion both an inflammatory environment and TCR ligation by its ligand. In contrast, MAIT cells are able to inhibit the proliferation of allospecific LT in vitro in a dose-dependent manner. Furthermore, the adoptive transfer of MAIT cells in a mouse model of xeno-GVHD resulted in a delay in early or late GvHD development. Altogether, these data describe a new regulatory function of MAIT cells in an allogeneic context, allowing us to consider their use in cell therapy to limit GvHD.
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