静脉、腹腔或瘤内注射 NK 细胞在人胰腺腺癌荷瘤小鼠中的急性毒性：随机研究

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 × 10 7 , 1 × 10 8 , and 5 × 10 8 cells/kg, respectively; mice in Groups 5-7 were injected with NK cells intraperitoneally at doses of 2 × 10 7 , 1 × 10 8 , and 5 × 10 8 cells/kg, respectively, and mice in Groups 8-10 with NK cells intratumorally at doses of 4 × 10 3 , 2 × 10 4 , and 1 × 10 5 cells/mm 3 , respectively. Each group was given a single dose; the mice were observed clinically, and body weight, food intake, blood biochemistry, and tumor volume were measured. 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 × 10 8 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 × 10 3 and 1 × 10 5 cells/mm 3 and female mice at the dose of 2 × 10 4 cells/mm 3 showed a decrease in extramedullary hematopoiesis of spleen, and female mice at a dose of 4 × 10 3 cells/mm 3 and mice of both sexes at doses of ≥ 2 × 10 4 cells/mm 3 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 × 10 4 cells/mm 3 , and inflammatory cell infiltration in liver was observed in mice of both sexes at a dose of 1 × 10 5 cells/mm 3 . No other abnormal changes with toxicological significance in clinical observation, body weight, food intake, or blood biochemistry were observed in each group.

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.