[NK-92 cells modified with chimeric antigen receptor targeting PD-L1 inhibits the proliferation of A549 lung cancer cells]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2022 Mar;38(3):212-217.
[Article in Chinese]

Abstract

Objective To investigate the anti-tumor activity of PD-L1-redirected chimeric antigen receptor modified NK-92 cells in lung cancer. Methods NK-92 cells modified by chimeric antigen receptor (pCAR-92) was obtained by lentivirus transfection. Tumor cells overexpressing PD-L1 were induced by IFN-γ. Lactic dehydrogenase (LDH) level was used cells to identify the cytotoxicity of pCAR-92 cells to target cells. The activation markers of CD107a and IFN-γ in pCAR-92 cells were detected by flow cytometry, and the anti-tumor activity of pCAR-92 cells in vivo was verified by xenograft model. Results Flow cytometry showed that the positive ratio of pCAR-92 cells ranged from 70% to 80%. The LDH detection showed that pCAR-92 cells could significantly lyse tumor cells induced by IFN-γ compared to control group. Flow cytometry for the expression of CD107a and IFN-γ showed that pCAR-92 cells could be significantly activated after co-incubation with tumor cells induced by IFN-γ. The tumor inhibitory effect of pCAR-92 cells was stronger than that of control group. In addition, after pCAR-92 cells treatment, the expression of PD-L1 in tumor decreased and the number of tumor infiltrating NK cells increased. Conclusion NK-92 cells modified with chimeric antigen receptors targeting PD-L1 have evident anti-tumor effects.

MeSH terms

  • A549 Cells
  • B7-H1 Antigen / genetics
  • Cell Proliferation
  • Humans
  • Lung Neoplasms* / pathology
  • Receptors, Chimeric Antigen* / genetics

Substances

  • B7-H1 Antigen
  • Receptors, Chimeric Antigen