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Poster session 14

760P - Acute toxicities of intravenous, intraperitoneal, or intratumoral injection of natural killer cells in human pancreatic adenocarcinoma-bearing mice: A randomized study

Date

10 Sep 2022

Session

Poster session 14

Presenters

Lei Huang

Citation

Annals of Oncology (2022) 33 (suppl_7): S331-S355. 10.1016/annonc/annonc1058

Authors

L. Huang

Author affiliations

  • Department Of Oncology, Ruijin Hospital - Shanghai Jiao Tong University School of Medicine, 200025 - Shanghai/CN
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Abstract 760P

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

L. Huang.

Funding

Jiangsu RE-STEM Biotechnology Co., Ltd., Soochow, China.

Disclosure

The author has declared no conflicts of interest.

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