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Authors Shi B, Sun AX, Zhang XR
Received 11 January 2018
Accepted for publication 23 March 2018
Published 8 May 2018 Volume 2018:11 Pages 2657—2672
DOI https://doi.org/10.2147/OTT.S162281
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 3
Editor who approved publication: Dr Carlos Vigil Gonzales
Purpose: In cytokine-induced killer (CIK) cell therapy, the phenotypes and the
numbers of CIK cells have a great influence on the therapeutic effects. This
study aimed to investigate the effects of different ex vivo cell culture
methods on the proliferation and cytotoxicity of CIK cells that were obtained
from gastric cancer patients.
Patients and
methods: CIK precursor (Pre-CIK) cells
were collected by either hydroxyethyl starch (HES) sedimentation (HES method,
unpurified group) or Ficoll-Hypaque density gradient centrifugation (Ficoll
method, purified group). Cell number, collection time, and morphology of
Pre-CIK cells in the two groups were determined. The proliferation ability,
cytokines, phenotypes, and cytotoxicity of CIK cells in the two groups were
evaluated ex vivo and in vivo.
Results: In this study, the number of Pre-CIK cells in the unpurified group was
significantly higher than that in the purified group (P <0.05). Numbers of
erythrocytes, platelets, and granulocytes were reduced significantly following
the purification step (P <0.05).
Compared to CIK cells in the purified group, those in the unpurified group
showed more active proliferation, accompanied by higher percentages of CD8+, CD3-CD56+, and CD3+CD56+ cells, which were responsible for cytotoxicity of CIK cells (P <0.05). This research also
showed that the levels of interferon-γ, interleukin-2, and tumor necrosis
factor-α, which can enhance the proliferation and cytotoxicity of CIK cells,
were significantly increased in the unpurified group (P <0.05). Furthermore, CIK cells
in the unpurified group also showed stronger anti-tumor effects against gastric
cancer cells than those in the purified group, both ex vivo and in vivo (P <0.05).
Conclusion: The removal of Ficoll-Hypaque purification step reduces the time and
cost of the Pre-CIK separation and provides more CIK cells with higher
cytotoxicity, which is of great importance in the clinical application of CIK
cell therapy.
Keywords: red blood cells, cytokine-induced killer cells, CIK precursor cells,
gastric cancer