Natural killer cell-based adoptive transfer immunotherapy for pancreatic ductal adenocarcinoma in a KrasLSL-G12D p53LSL-R172H Pdx1-Cre mouse model

Am J Cancer Res. 2019 Aug 1;9(8):1757-1765. eCollection 2019.


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 KrasLSL-G12D p53LSL-R172H Pdx1-Cre (KPC) mice were used to evaluate the therapeutic efficacy. Mouse NK cells (LNK cells) (1×106) 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 in vitro. LNK-cell adoptive transfer therapy elicited potent in vivo antitumor activity, resulting in delayed tumor growth (P=0.033) in KPC mice. The ADC values at the last timepoint ((0.94±0.06)×10-3 mm2/s) were significantly higher than that at first timepoint ((0.75±0.04)×10-3 mm2/s) in treated tumors (P<0.001). ADC values were significantly different between control group and treated tumors at the last time point ((0.75±0.09)×10-3 mm2/s vs (0.94±0.06)×10-3 mm2/s, P=0.004) in KPC mice. Our data demonstrate the potential of NK cell-based adoptive transfer immunotherapy for PDAC treatment.

Keywords: Natural killer cell; immunotherapy; magnetic resonance imaging; pancreatic cancer.