The safety profiles of natural killer (NK) cell infusion in pancreatic adenocarcinoma (PaC) remain largely unclear and need to be further comprehensively clarified before future in-human investigations are conducted.
100 NPG tumor-bearing mice (50/sex) were engrafted subcutaneously with human PaC BXPC-3 cells 9 days before administration. They were randomly divided into 10 groups with 5 males and 5 females in each group. Mice in Group 1 were given sodium chloride intravenously as vehicle control, and mice in Groups 2-4 human peripheral blood-derived NK cells intravenously at doses of 2×107, 1×108, and 5×108 cells/kg, respectively; mice in Groups 5-7 were injected with NK cells intraperitoneally at doses of 2×107, 1×108, and 5×108 cells/kg, respectively, and mice in Groups 8-10 with NK cells intratumorally at doses of 4×103, 2×104, and 1×105 cells/mm3, respectively. Each group was given a single dose. On Day 15, the mice were euthanized for gross anatomy and histopathology.
On planned euthanasia, in Groups 2-4 no gross or microscopic pathological changes related to cells injection were found; in Groups 5-7 mice of both sexes showed a decrease in extramedullary hematopoiesis of spleen, and at the dose of 5×108 cells/kg, mice of both sexes showed an increase in the composition of spleen white pulp cells. In Groups 8-10, mice of both sexes at doses of 4×103 and 1×105 cells/mm3 and female mice at the dose of 2×104 cells/mm3 showed a decrease in extramedullary hematopoiesis of spleen, and female mice at a dose of 4×103 cells/mm3 and mice of both sexes at doses of ≥2×104 cells/mm3 showed an increase in the composition of spleen white pulp cells; perivascular/peribronchiolar inflammatory cell infiltration in lung and bronchus was observed in mice of both sexes at doses of ≥2×104 cells/mm3, and inflammatory cell infiltration in liver was observed in mice of both sexes at a dose of 1×105 cells/mm3.
In our study intravenous injection appears the safest way to give NK cells to human PaC-bearing mice. Using intraperitoneal or intratumoral administration, spleen, liver, and lung were the most often affected organs, albeit with mostly mild pathological changes.
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Legal entity responsible for the study
Jiangsu RE-STEM Biotechnology Co., Ltd., Soochow, China.
The author has declared no conflicts of interest.