更新于：2024-11-01

SLAMF2 x Interleukins x 4-1BBL

更新于：2024-11-01

基本信息

关联

项与 SLAMF2 x Interleukins x 4-1BBL 相关的药物

CN117089523

专利挖掘

靶点

4-1BBL x Interleukins x SLAMF2

作用机制-

在研机构

上海怀越生物科技有限公司

原研机构

上海怀越生物科技有限公司

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 SLAMF2 x Interleukins x 4-1BBL 相关的临床结果

登录后查看更多信息

100 项与 SLAMF2 x Interleukins x 4-1BBL 相关的转化医学

登录后查看更多信息

0 项与 SLAMF2 x Interleukins x 4-1BBL 相关的专利（医药）

登录后查看更多信息

项与 SLAMF2 x Interleukins x 4-1BBL 相关的文献（医药）

2023-10-01·Cytotherapy

2B4 inhibits the apoptosis of natural killer cells through phosphorylated extracellular signal-related kinase/B-cell lymphoma 2 signal pathway

Article

作者: Tian, Zheng ; Xing, Haiyan ; Tang, Kejing ; Rao, Qing ; Wang, Min ; Huang, Qianqian ; Qiu, Shaowei ; Liu, Yu ; Xu, Yingxi ; Mou, Junli ; Zhou, Tong ; Wang, Jianxiang ; Xie, Leling

BACKGROUND AIMSDecades after the identification of natural killer (NK) cells as potential effector cells against malignantly transformed cells, an increasing amount of research suggests that NK cells are a prospective choice of immunocytes for cancer immunotherapy in addition to T lymphocytes for cancer immunotherapy. Recent studies have led to a breakthrough in the combination of hematopoietic stem-cell transplantation with allogeneic NK cells infusion for the treatment of malignant tumors. However, the short lifespan of NK cells in patients is the major impediment, limiting their efficacy. Therefore, prolonging the survival of NK cells will promote the application of NK-cell immunotherapy. As we have known, NK cells use a "missing-self" mechanism to lyse target cells and exert their functions through a wide array of activating, co-stimulatory and inhibitory receptors. Our previous study has suggested that CD244 (2B4), one of the co-stimulatory receptors, can improve the function of chimeric antigen receptor NK cells. However, the underlying mechanism of how 2B4 engages in the function of NK cells requires further investigation. Overall, we established a feeder cell with the expression of CD48, the ligand of 2B4, to investigate the function of 2B4-CD48 axis in NK cells, and meanwhile, to explore whether the newly generated feeder cell can improve the function of ex vivo-expanded NK cells.METHODSFirst, K562 cells overexpressing 4-1BBL and membrane-bound IL-21 (mbIL-21) were constructed (K562-41BBL-mbIL-21) and were sorted to generate the single clone. These widely used feeder cells (K562-41BBL-mbIL-21) were named as Basic Feeder hereinafter. Based on the Basic feeder, CD48 was overexpressed and named as CD48 Feeder. Then, the genetically modified feeder cells were used to expand primary NK cells from peripheral blood or umbilical cord blood. In vitro experiments were performed to compare proliferation ability, cytotoxicity, survival and activation/inhibition phenotypes of NK cells stimulated via different feeder cells. K562 cells were injected into nude mice subcutaneously with tail vein injection of NK cells from different feeder system for the detection of NK in vivo persistence and function.RESULTSCompared with Basic Feeders, CD48 Feeders can promote the proliferation of primary NK cells from peripheral blood and umbilical cord blood and reduce NK cell apoptosis by activating the p-ERK/BCL2 pathway both in vitro and in vivo without affecting overall phenotypes. Furthermore, NK cells expanded via CD48 Feeders showed stronger anti-tumor capability and infiltration ability into the tumor microenvironment.CONCLUSIONSIn this preclinical study, the engagement of the 2B4-CD48 axis can inhibit the apoptosis of NK cells through the p-ERK/BCL2 signal pathway, leading to an improvement in therapeutic efficiency.

2016-02-01·European Journal of Immunology3区 · 医学

CD252 regulates mast cell mediated, CD1d‐restricted NKT‐cell activation in mice

3区 · 医学

Article

作者: Orinska, Zane ; Ewers, Hanno ; Bulfone‐Paus, Silvia ; Gonzalez Roldan, Nestor

The interaction between tissue‐resident mast cells (MCs) and recruited immune cells contributes to tissue immunosurveillance. However, the cells, mechanisms, and receptors involved in this crosstalk remain ill defined. Invariant natural killer T (iNKT) cells are CD1d‐restricted innate lymphocytes that recognize glycolipid antigens and have emerged as critical players in immunity. Here, we show that primary mouse peritoneal MCs express surface CD1d, which is upregulated in vivo following administration of alpha‐galactosylceramide. In contrast, in BM‐derived MCs CD1d was found to be stored intracellularly and to relocate at the cell surface upon IgE‐mediated degranulation. Activated BM‐derived MCs expressing surface CD1d and loaded with alpha‐galactosylceramide were found to induce iNKT‐cell proliferation and the release of IFN‐γ, IL‐13, and IL‐4 in a CD1d‐restricted manner. Moreover, the costimulatory molecules CD48, CD137L, CD252, CD274, and CD275 affected MC‐induced IFN‐γ release and iNKT‐cell proliferation. Interestingly, among the costimulatory molecules, CD48 and CD252 exhibited a distinctly regulatory activity on iNKT‐cell release of both IFN‐γ and IL‐13. In conclusion, we demonstrate that the crosstalk between MCs and iNKT cells may regulate inflammatory immune responses.

Frontiers in Immunology2区 · 医学

GMP-Compliant Universal Antigen Presenting Cells (uAPC) Promote the Metabolic Fitness and Antitumor Activity of Armored Cord Blood CAR-NK Cells

2区 · 医学

ArticleOA

作者: Rezvani, Katayoun ; Ensley, Emily L ; Tong, Yijiu ; Shpall, Elizabeth J ; Chen, Ken ; Kerbauy, Lucila ; Lin, Paul ; Uprety, Nadima ; Ang, Sonny O T ; Nunez Cortes, Ana Karen ; Liu, Enli ; Basar, Rafet ; Mohanty, Vakul ; Li, Ye ; Champlin, Richard E ; Acharya, Sunil ; Kaur, Indreshpal ; Banerjee, Pinaki P ; Reyes Silva, Francia ; Daher, May ; Li, Li ; Kaplan, Mecit ; Shanley, Mayra ; Shaim, Hila ; Yang, Ryan Z ; Muniz-Feliciano, Luis

Natural killer (NK) cells are innate lymphocytes recognized for their important role against tumor cells. NK cells expressing chimeric antigen receptors (CARs) have enhanced effector function against various type of cancer and are attractive contenders for the next generation of cancer immunotherapies. However, a number of factors have hindered the application of NK cells for cellular therapy, including their poorin vitrogrowth kinetics and relatively low starting percentages within the mononuclear cell fraction of peripheral blood or cord blood (CB). To overcome these limitations, we genetically-engineered human leukocyte antigen (HLA)-A−and HLA-B−K562 cells to enforce the expression of CD48, 4-1BBL, and membrane-bound IL-21 (mbIL21), creating a universal antigen presenting cell (uAPC) capable of stimulating their cognate receptors on NK cells. We have shown that uAPC can drive the expansion of both non-transduced (NT) and CAR-transduced CB derived NK cells by >900-fold in 2 weeks of co-culture with excellent purity (>99.9%) and without indications of senescence/exhaustion. We confirmed that uAPC-expanded research- and clinical-grade NT and CAR-transduced NK cells have higher metabolic fitness and display enhanced effector function against tumor targets compared to the corresponding cell fractions cultured without uAPCs. This novel approach allowed the expansion of highly pure GMP-grade CAR NK cells at optimal cell numbers to be used for adoptive CAR NK cell-based cancer immunotherapy.