Details

Autor(en) / Beteiligte

• Cao, Bihui
• Liu, Manting
• Wang, Lu
• Liang, Baoxia
• Feng, Yunfei
• Chen, Xiaopei
• Shi, Yuanyuan
• Zhang, Jinling
• Ye, Xiaodie
• Tian, Yu
• Zhi, Cheng
• Li, Junping
• Lian, Hui
• Wu, Qingde
• Zhang, Zhenfeng

Titel

Use of chimeric antigen receptor NK-92 cells to target mesothelin in ovarian cancer

Ist Teil von

• Biochemical and biophysical research communications, 2020-03, Vol.524 (1), p.96-102

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Mesothelin (MSLN) has been reported to be overexpressed in ovarian cancer and may be an ideal target for immunotherapy. Recent studies have suggested that natural killer (NK) cells may be better chimeric antigen receptor (CAR) drivers because of their favorable innate characteristics, such as directly recognizing and killing tumor cells, resulting in a graft-versus-tumor effect but irresponsible for graft-versus-host disease (GVHD). The therapeutic effects of CAR-engineered NK cells targeting MSLN in ovarian cancer have not been evaluated. In this study, MSLN- and CD19-targeted CAR NK-92 (MSLN- and CD19-CAR NK) cells were constructed. Both MSLN- and CD19-CAR molecules were highly expressed on the surface of NK-92 cells following lentiviral gene transduction. MSLN-CAR NK cells specifically killed MSLN-positive ovarian cancer cells (OVCAR-3 and SK-OV-3), rather than MSLN-negative cells (SK-HEP-1), in vitro. Moreover, compared with parental NK-92 cells and CD19-CAR NK cells, stronger cytokine secretion was detected in MSLN-CAR NK cells cocultured with OVCAR-3 and SK-OV-3. Furthermore, MSLN-CAR NK cells effectively eliminated ovarian cancer cells in both subcutaneous and intraperitoneal tumor models; these cells also significantly prolonged the survival of intraperitoneally tumor-bearing mice. These results demonstrate that MSLN-CAR NK cells have robust specific antitumor activity, both in vitro and in vivo, suggesting that mesothelin could be a potential target for CAR NK cells and could be applied in the treatment of ovarian cancer. •Mesothelin is overexpressed in ovarian cancer.•NK-92 cells can be modified to express a chimeric antigen receptor targeting mesothelin.•Mesothelin CAR NK-92 cells specifically target mesothelin-positive cancer cell lines.•Mesothelin CAR NK-92 cells represent antitumor activity against ovarian cancer tumor models.