Regnase-1(Ribometrix)(Regnase-1(Ribometrix)) - 药物靶点：regnase-1_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

化学药

别名-

靶点

regnase-1

作用机制

regnase-1抑制剂(zinc finger CCCH-type containing 12A inhibitors)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Ribometrix, Inc.初创企业

在研机构

Ribometrix, Inc.初创企业

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 Regnase-1(Ribometrix) 相关的临床结果

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100 项与 Regnase-1(Ribometrix) 相关的转化医学

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100 项与 Regnase-1(Ribometrix) 相关的专利（医药）

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1

项与 Regnase-1(Ribometrix) 相关的文献（医药）

2024-06-01·Immunity

Deletion of the mRNA endonuclease Regnase-1 promotes NK cell anti-tumor activity via OCT2-dependent transcription of Ifng

Article

作者: Kozakai, Yuuki ; Tanaka, Hiroki ; Diez, Diego ; Motooka, Daisuke ; Fukui, Eriko ; Nabeshima, Hiroshi ; Akira, Shizuo ; Sun, Xin ; Nagahama, Yasuharu ; Singh, Shailendra Kumar ; Vivier, Eric ; Fukushima, Kiyoharu

Limited infiltration and activity of natural killer (NK) and T cells within the tumor microenvironment (TME) correlate with poor immunotherapy responses. Here, we examined the role of the endonuclease Regnase-1 on NK cell anti-tumor activity. NK cell-specific deletion of Regnase-1 (Reg1^ΔNK) augmented cytolytic activity and interferon-gamma (IFN-γ) production in vitro and increased intra-tumoral accumulation of Reg1^ΔNK-NK cells in vivo, reducing tumor growth dependent on IFN-γ. Transcriptional changes in Reg1^ΔNK-NK cells included elevated IFN-γ expression, cytolytic effectors, and the chemokine receptor CXCR6. IFN-γ induced expression of the CXCR6 ligand CXCL16 on myeloid cells, promoting further recruitment of Reg1^ΔNK-NK cells. Mechanistically, Regnase-1 deletion increased its targets, the transcriptional regulators OCT2 and IκBζ, following interleukin (IL)-12 and IL-18 stimulation, and the resulting OCT2-IκBζ-NF-κB complex induced Ifng transcription. Silencing Regnase-1 in human NK cells increased the expression of IFNG and POU2F2. Our findings highlight NK cell dysfunction in the TME and propose that targeting Regnase-1 could augment active NK cell persistence for cancer immunotherapy.

100 项与 Regnase-1(Ribometrix) 相关的药物交易

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