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Xiao, Lin; Cen, Dongzhi; Gan, Haining; Sun, Yan; Huang, Nanqi; Xiong, Hanzhen; Jin, Qiongmei; Su, Liqun; Liu, Xuejuan; Wang, Kejian; Yan, Guangrong; Dong, Tianfa; Wu, Shangbiao; Zhou, Pengzhi; Zhang, Jinshan; Liang, Weixiang; Ren, Junlan; Teng, Yaoshu; Chen, Can; Xu, Xue Hu
Molecular therapy, 06/2019, Letnik: 27, Številka: 6Journal Article
By fusing the extracellular domain of the natural killer (NK) cell receptor NKG2D to DAP12, we constructed a chimeric antigen receptor (CAR) to improve NK cell tumor responses. An RNA electroporation approach that provides transient expression of the CAR was adopted as a risk mitigation strategy. Expression of the NKG2D RNA CAR significantly augmented the cytolytic activity of NK cells against several solid tumor cell lines in vitro and provided a clear therapeutic benefit to mice with established solid tumors. Three patients with metastatic colorectal cancer were then treated with local infusion of the CAR-NK cells. Reduction of ascites generation and a marked decrease in number of tumor cells in ascites samples were observed in the first two patients treated with intraperitoneal infusion of low doses of the CAR-NK cells. The third patient with metastatic tumor sites in the liver was treated with ultrasound-guided percutaneous injection, followed by intraperitoneal infusion of the CAR-NK cells. Rapid tumor regression in the liver region was observed with Doppler ultrasound imaging and complete metabolic response in the treated liver lesions was confirmed by positron emission tomography (PET)- computed tomographic (CT) scanning. Our results highlight a promising therapeutic potential of using RNA CAR-modified NK cells to treat metastatic colorectal cancer. Xiao et al. have developed a new type of CAR-NK cells specific to NKG2D ligands. Local infusion of these cells into patients with metastatic colorectal cancer shows clinical benefits in controlling malignant ascites and reducing tumor burden, highlighting a promising therapeutic potential of CAR-NK cells to treat solid tumors.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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