更新于：2024-11-01

IL-12R x IL15R

更新于：2024-11-01

基本信息

关联

项与 IL-12R x IL15R 相关的药物

VG-203

靶点

IL-12R x IL15R

作用机制

IL-12R刺激剂 [+1]

在研机构

Virogin Biotech Ltd.初创企业 [+1]

原研机构

Virogin Biotech Ltd.初创企业

在研适应症

实体瘤 [+3]

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

SON-1210

靶点

IL-12R x IL15R

作用机制

IL-12R刺激剂 [+2]

在研机构

Sonnet BioTherapeutics, Inc.

原研机构

Sonnet BioTherapeutics, Inc.

在研适应症

胰腺癌 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

HCW-9201

靶点

IL-12R x IL15R x IL18R1

作用机制

IL-12R刺激剂 [+3]

在研机构-

原研机构

HCW Biologics Inc.

在研适应症-

非在研适应症

急性髓性白血病 [+1]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 IL-12R x IL15R 相关的临床结果

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100 项与 IL-12R x IL15R 相关的转化医学

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0 项与 IL-12R x IL15R 相关的专利（医药）

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项与 IL-12R x IL15R 相关的文献（医药）

2021-11-15·Cancer Biology & Medicine2区 · 医学

EZH2 identifies the precursors of human natural killer cells with trained immunity

2区 · 医学

ArticleOA

作者: Ren, Xiubao ; Zhang, Hong ; Zhao, Qiang ; Zhang, Xuzhen ; Li, Long ; Yin, Jie ; Zhang, Chen ; Yu, Wenwen ; Zheng, Jian ; Zhou, Kaichen ; Wang, Yang ; Sun, Qian ; Hu, Jiajian ; Xiao, Jun ; Su, Yudong ; Zhang, Yingchi ; Wei, Feng

Objective: Trained immunity of natural killer (NK) cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods after preactivation. However, the human NK cells responsible for the generation and maintenance of trained immunity are largely unknown. We hypothesized that heterogeneous human NK cells would respond differentially to stimulation with a combination of IL-12, IL-15, and IL-18, and that an NK cell subset might exist that is mainly responsible for the induction of trained immunity. On the basis of our hypothesis, we aimed to identify the subset from which cytokine-trained human NK cells originate and to explore possible regulatory targets for drug intervention. Methods: Flow cytometry assays were performed to analyze the functions of cytokine-trained NK cells and examine cell division and protein expression in NK cell subsets. Single-cell RNA sequencing (scRNA-seq) plus TotalSeq™ technology was used to track the heterogeneity of NK cells during the induction of trained immunity. Results: Traditional developmental markers for peripheral NK cells were unable to identify the precursors of human NK cells with trained immunity. Therefore, we used scRNA-seq plus TotalSeq™ technology to track the heterogeneity of NK cells during the induction of trained immunity and identified a unique cluster of CD57-NKG2A+EZH2+IFNG+MKI67+IL12R+IL15R+IL18R+ NK cells. Enrichment and pseudotime trajectory analyses suggested that this cluster of NK cells contained the precursor of trained NK cells. We then used flow cytometry to further investigate the role of EZH2 in trained NK precursors and found that CD57-NKG2A+EZH2+ NK cells had faster cell cycles and an enhanced trained phenotype, and EZH2 inhibition significantly impaired the induction of trained immunity in NK cells. These results suggested that EZH2 is a unique epigenetic marker of precursors of human NK cells with trained immunity. Conclusions: Our work revealed human NK heterogeneity in the induction of trained immunity, identified the precursor subset for trained NK cells, and demonstrated the critical role of EZH2 in the induction of trained immunity in human NK cells.

Nature Communications1区 · 综合性期刊

Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals

1区 · 综合性期刊

ArticleOA

作者: Reddy, Srija ; Zhang, Shimeng ; Zhong, Xiao-Ping ; Pan, Yun ; Xie, Jinhai ; Sleasman, John W ; Wang, Peng ; Chu, Shuai ; Li, Lei ; Tao, Huishan

AbstractMucosal-associated invariant T (MAIT) cells have important functions in immune responses against pathogens and in diseases, but mechanisms controlling MAIT cell development and effector lineage differentiation remain unclear. Here, we report that IL-2/IL-15 receptor β chain and inducible costimulatory (ICOS) not only serve as lineage-specific markers for IFN-γ-producing MAIT1 and IL-17A-producing MAIT17 cells, but are also important for their differentiation, respectively. Both IL-2 and IL-15 induce mTOR activation, T-bet upregulation, and subsequent MAIT cell, especially MAIT1 cell, expansion. By contrast, IL-1β induces more MAIT17 than MAIT1 cells, while IL-23 alone promotes MAIT17 cell proliferation and survival, but synergizes with IL-1β to induce strong MAIT17 cell expansion in an mTOR-dependent manner. Moreover, mTOR is dispensable for early MAIT cell development, yet pivotal for MAIT cell effector differentiation. Our results thus show that mTORC2 integrates signals from ICOS and IL-1βR/IL-23R to exert a crucial role for MAIT17 differentiation, while the IL-2/IL-15R-mTORC1-T-bet axis ensures MAIT1 differentiation.