Study On Prostate Cancer Therapy With PSMA-CAR-NK92

Prostate cancer is the most common male malignant tumor in the world,and its morbidity and mortality are still very high.At present,standard treatments for prostate cancer include surgical resection,radiation therapy and hormonal therapy,but these treatments are accompanied by obvious side effects.In the past few years,immunotherapy as an alternative has received more and more attention.Chimeric antigen receptor immune cells have been widely applied into acute lymphoblastic leukemia,and has achieved significant clinical results.As innate immune effectors,NK cells can produce rapid cytotoxicity on cancer cells and virus-infected cells without prior sensitization and kill target cells in a nonspecific manner,and hopefully become the next chimeric antigen receptor immune cell.In principle,the chimeric antigen receptor NK cells greatly reduce the risk of tumor disease recurrence and side effects,and have the hope of producing allogeneic products.In the current study,we explored anti-prostate cancer with CAR-NK92 cells to target PSMA,which is the specific antigen for prostate cancer.Firstly,we constructed lentivirus vector and packaged letiviruses.PSMA-CAR-NK92 cells were prepared by infecting NK92 cells and the cytotoxicity of PSMA-CAR-NK92 against established prostate cancer cell lines in vitro was studied.The results showe that PSMA-CARNK92 cells could kill prostate tumor cells more effectively and more selectively than NK92 cell.Also,the release of cytokines and cytotoxicity of PSMA-CAR-NK92 cells depended on the existence of target antigen PSMA.Then,we used a human prostate cancer cell xenograft model to investigated the in vivo anti-tumor effects of PSMACAR-NK92 cells in severe combined immunodeficient mice.The results indicated that PSMA-CAR-NK92 cell therapy could effectively inhibit the growth of tumor in vivo.Lastly,we prepared PSMA-CAR-NK92 cells with overexpression of IL-21.The in vitro experiment showed that IL-21 could promote the cell proliferation and cytotoxicity of PSMA-CAR-NK92 cells,which laid the experimental basis on the preparation of novel PSMA-CAR-NK92 cells for cell therapy on prostate cancer.