Last update 01 Nov 2024

CXCR2 x GPC3

Last update 01 Nov 2024

Basic Info

Related Targets

CXCR2GPC3

Drugs associated with CXCR2 x GPC3

HX-s002

Target

CXCR2 x GPC3

Mechanism

CXCR2 antagonists [+3]

Active Org.

Huaxia Yingtai Beijing Biotechnology Co Ltd.Startup

Originator Org.

Huaxia Yingtai Beijing Biotechnology Co Ltd.Startup

Active Indication

Liver Cancer [+1]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CXCR2 x GPC3

100 Translational Medicine associated with CXCR2 x GPC3

0 Patents (Medical) associated with CXCR2 x GPC3

Literatures (Medical) associated with CXCR2 x GPC3

Journal of Translational Medicine

Radiotherapy enhances the anti-tumor effect of CAR-NK cells for hepatocellular carcinoma

Article

Author: Zhang, Han ; Zhang, Yuqin ; Ling, Jing ; Xie, Guozhu ; Chen, Ying ; Liu, Zishen ; Wang, Kunyuan ; Dong, Xin ; Wang, Fei ; Guo, Yuetong ; Xie, Qiankun ; Guo, Zhaoze ; Sun, Yao ; Lin, Xiaotong ; Sugimura, Ryohichi ; Xiang, Hongjin

BACKGROUNDChimeric antigen receptor (CAR)-NK cell therapy has shown remarkable clinical efficacy and safety in the treatment of hematological malignancies. However, this efficacy was limited in solid tumors owing to hostile tumor microenvironment (TME). Radiotherapy is commonly used for solid tumors and proved to improve the TME. Therefore, the combination with radiotherapy would be a potential strategy to improve therapeutic efficacy of CAR-NK cells for solid tumors.METHODSGlypican-3 (GPC3) was used as a target antigen of CAR-NK cell for hepatocellular carcinoma (HCC). To promote migration towards HCC, CXCR2-armed CAR-NK92 cells targeting GPC3 were first developed, and their cytotoxic and migration activities towards HCC cells were evaluated. Next, the effects of irradiation on the anti-tumor activity of CAR-NK92 cells were assessed in vitro and in HCC-bearing NCG mice. Lastly, to demonstrate the potential mechanism mediating the sensitized effect of irradiation on CAR-NK cells, the differential gene expression profiles induced by irradiation were analyzed and the expression of some important ligands for the NK-cell activating receptors were further determined by qRT-PCR and flow cytometry.RESULTSIn this study, we developed CXCR2-armed GPC3-targeting CAR-NK92 cells that exhibited specific and potent killing activity against HCC cells and the enhanced migration towards HCC cells. Pretreating HCC cells with irradiation enhanced in vitro anti-HCC effect and migration activity of CXCR2-armed CAR-NK92 cells. We further found that only high-dose (8 Gy) but not low-dose (2 Gy) irradiation in one fraction could significantly enhanced in vivo anti-HCC activity of CXCR2-armed CAR-NK92 cells. Irradiation with 8 Gy significantly up-regulated the expression of NK cell-activating ligands on HCC cells.CONCLUSIONSOur results indicate the evidence that irradiation could efficiently enhance the anti-tumor effect of CAR-NK cells in solid tumor model. The combination with radiotherapy would be an attractive strategy to improve therapeutic efficacy of CAR-NK cells for solid tumors.

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