3. ANTI-CANCER EFFECT OF NATURAL KILLER CELLS IN AN IMMUNODEFICIENT MOUSE MODEL BEARING HUMAN LUNG CANCER TUMOR

Nguyen Thi Thuy Mau1, Tran Van Khanh1, Nguyen Linh Toan2, Tran Van Chieu1, Nguyen Thanh Binh1, Tran Huy Thinh1
1 Hanoi Medical University
2 Vietnam Military Medical University

Main Article Content

Abstract

Objectives: To evaluate the anti-cancer effect of natural killer cells in an immunodeficient mouse
model bearing human lung cancer tumor (H460 lineage).
Objects and methods: Natural killer (NK) cells were activated, differentiated, and proliferated in the
laboratory until a concentration of at least 107 cells/ml was reached. Immune-deficient mice (nude
mice) 6 - 8 weeks old, number of 24 animals, were injected with 106 H460 lineage human lung cancer
cells under the skin of the thigh to create human lung cancer in nude mice. When the tumor size was
about 50 - 70mm3 (after 10 days of transplantation), mice were divided into 4 groups (6 animals/
group), the treatment groups were injected with NK cells through the tail vein with a dose of 106
cells per 10g, 5x106 cells per 10g and 107 cells per 10g, respectively, once a week, for 3 consecutive
weeks, the control group was injected with 0,9% NaCl containing 5% human albumin.
Results: The group of mice with H460 human lung cancer treated with NK cells had a smaller tumor
volume, a longer survival time and a lower death rate than the control group with p>0,05 due to small
sample size.
Conclusion: The study suggests that natural killer cells were effective against human lung cancer in
an immune-deficient mouse model of xenograft cancer.

Article Details

References

[1] Siegel RL, Miller KD, Fuchs HE et al., Cancer
statistics, 2022. CA: A Cancer Journal for
Clinicians, 72(1), 7–33. https://doi.org/10.3322/
caac.21708, 2022.
[2] Sung H, Ferlay J, Siegel RL et al., Global
Cancer Statistics 2020: GLOBOCAN Estimates
of Incidence and Mortality Worldwide for 36
Cancers in 185 Countries. CA: a cancer journal
for clinicians, 71(3), 209–249. https://doi.
org/10.3322/caac.21660, 2021.
[3] Pignon JP, Tribodet H, Scagliotti GV et al.,
Lung adjuvant cisplatin evaluation: a pooled
analysis by the LACE Collaborative Group.
Journal of Clinical Oncology: Official Journal
of the American Society of Clinical Oncology,
26(21), 3552–3559. https://doi.org/10.1200/
JCO.2007.13.9030, 2008.
[4] Torre LA, Siegel RL, Jemal A et al., Lung Cancer
Statistics. In A. Ahmad & S. Gadgeel (Eds.),23
Lung Cancer and Personalized Medicine: Current
Knowledge and Therapies (pp. 1–19). Cham:
Springer International Publishing. https://doi.
org/10.1007/978-3-319-24223-1_1, 2016.
[5] Kay HD, Fagnani R, Bonnard GD, Cytotoxicity
against the K562 erythroleukemia cell line by
human natural killer (NK) cells which do not bear
free Fc receptors for IgG. International Journal of
Cancer, 24(2), 141–150. https://doi.org/10.1002/
ijc.2910240204, 1979.
[6] Diefenbach A, Jensen ER, Jamieson AM et al.,
Rae1 and H60 ligands of the NKG2D receptor
stimulate tumour immunity. Nature, 413(6852),
165–171. https://doi.org/10.1038/35093109,
2001.
[7] Motohashi S, Ishikawa A, Ishikawa E et al., A
phase I study of in vitro expanded natural killer T
cells in patients with advanced and recurrent nonsmall cell lung cancer. Clinical Cancer Research:
An Official Journal of the American Association
for Cancer Research, 12(20 Pt 1), 6079–6086.
https://doi.org/10.1158/1078-0432.CCR-06-
0114, 2006.
[8] PhD Butterfield LH, FACS Kaufman HL, FACS
Marincola FM,Cancer Immunotherapy Principles
and Practice, Second Edition (2nd edition.).
Demos Medical, 2021.
[9] Guillerey C, Huntington ND, Smyth MJ, Targeting
natural killer cells in cancer immunotherapy.
Nature Immunology, 17(9), 1025–1036. https://
doi.org/10.1038/ni.3518, 2016.
[10] Cheng M, Chen Y, Xiao W et al., NK cell-based
immunotherapy for malignant diseases. Cellular
& Molecular Immunology, 10(3), 230–252.
https://doi.org/10.1038/cmi.2013.10, 2013.
[11] Roder JC, Haliotis T, Klein M et al., A new
immunodeficiency disorder in humans involving
NK cells. Nature, 284(5756), 553–555. https://
doi.org/10.1038/284553a0, 1980.
[12] Takeda K, Nakayama M, Sakaki M et al., IFN-γ
production by lung NK cells is critical for the
natural resistance to pulmonary metastasis of
B16 melanoma in mice. Journal of Leukocyte
Biology, 90(4), 777–785. https://doi.org/10.1189/
jlb.0411208, 2011.
[13] Jin S, Deng Y, Hao JW et al., NK Cell Phenotypic
Modulation in Lung Cancer Environment. PLOS
ONE, 9(10), e109976. https://doi.org/10.1371/
journal.pone.0109976, 2014.
[14] Wang F, Dong X, Wang J et al., Allogeneic
Expanded Human Peripheral NK Cells Control
Prostate Cancer Growth in a Preclinical Mouse
Model of Castration-Resistant Prostate Cancer.
Journal of Immunology Research, 2022, e1786395.
https://doi.org/10.1155/2022/1786395, 2022.
[15] JUNG IH, KIM DH, YOO DK et al., In Vivo
Study of Natural Killer (NK) Cell Cytotoxicity
Against Cholangiocarcinoma in a Nude Mouse
Model. In Vivo, 32(4), 771–781. https://doi.
org/10.21873/invivo.112307.