CXCR1 Expression to Improve Anti-Cancer Efficacy of Intravenously Injected CAR-NK Cells in Mice with Peritoneal Xenografts
Autor: | Yu Yang Ng, Johan Chin-Kang Tay, Shu Wang |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cancer Research NK Transgene mRNA lcsh:RC254-282 Article NKG2D 03 medical and health sciences Chemokine receptor 0302 clinical medicine Immune system trafficking Medicine Pharmacology (medical) Cytotoxicity CXCR1 business.industry coexpression tumor homing medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Chimeric antigen receptor CAR 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Molecular Medicine business Ovarian cancer Infiltration (medical) |
Zdroj: | Molecular Therapy: Oncolytics, Vol 16, Iss, Pp 75-85 (2020) Molecular Therapy Oncolytics |
ISSN: | 2372-7705 |
Popis: | One reason underlying the failure of current chimeric antigen receptor (CAR) immune therapy to treat solid tumors adequately is insufficient tumor infiltration of CAR immune cells. To address the issue, we electroporated natural killer (NK) cells with two mRNA constructs encoding the chemokine receptor CXCR1 and a CAR targeting tumor-associated NKG2D ligands. The CXCR1-modified NK cells displayed increased migration toward tumor supernatants in vitro and augmented infiltration into human tumors in vivo in subcutaneous and intraperitoneal xenograft models. Most importantly, the cytotoxicity of the CAR-NK cells was not affected by CXCR1 transgene expression, and the enhanced tumor trafficking following intravenous injection resulted in significantly increased antitumor responses in mice carrying established peritoneal ovarian cancer xenografts. Collectively, our findings suggest that the coexpression of CXCR1 and a CAR may provide a novel strategy to enhance therapeutic efficacy of NK cells against solid cancers. Keywords: trafficking, tumor homing, CXCR1, NKG2D, CAR, mRNA, NK, coexpression |
Databáze: | OpenAIRE |
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