Natural killer cell-based adoptive transfer immunotherapy for pancreatic ductal adenocarcinoma in a mouse model.

Natural killer (NK) cells play a pivotal role in host immunity against different malignancies, including pancreatic ductal adenocarcinoma (PDAC). Our study aimed to evaluate the antitumor effects of NK cell-based adoptive transfer immunotherapy for PDAC in an orthotopic mouse model. Orthotopic (KPC) mice were used to evaluate the therapeutic efficacy. Mouse NK cells (LNK cells) (1×10) were intravenously injected to tumor-bearing mice once a week for 3 weeks. MRI measurements (tumor volume and apparent diffusion coefficient (ADC) values) and survival were compared between control and LNK treated tumors. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to determine LNK cells cytotoxicity and IFN-γ level, respectively. LNK cells can produce a higher level of IFN-γ and more effectively lyse PDAC cells compared with spleen NK cells . LNK-cell adoptive transfer therapy elicited potent antitumor activity, resulting in delayed tumor growth (=0.033) in KPC mice. The ADC values at the last timepoint ((0.94±0.06)×10 mm/s) were significantly higher than that at first timepoint ((0.75±0.04)×10 mm/s) in treated tumors (<0.001). ADC values were significantly different between control group and treated tumors at the last time point ((0.75±0.09)×10 mm/s vs (0.94±0.06)×10 mm/s, =0.004) in KPC mice. Our data demonstrate the potential of NK cell-based adoptive transfer immunotherapy for PDAC treatment.