Back to Journals » OncoTargets and Therapy » Volume 11

Influence of different ex vivo cell culture methods on the proliferation and anti-tumor activity of cytokine-induced killer cells from gastric cancer patients

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 E Vigil


Bin Shi,1 Aixia Sun,2 Xiaorui Zhang3

1Department of Gastrointestinal Surgery, Liaocheng People’s Hospital of Taishan Medical University, Liaocheng, Shandong Province, China; 2Department of Clinical Laboratory, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong Province, China; 3Department of Health, Liaocheng People’s Hospital of Taishan Medical University, Liaocheng, Shandong Province, China

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
 

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]