Cytokine-Induced Killer Cells as an Adoptive Cellular Immunotherapy Strategy for Hepatocellular Carcinoma
Biochemistry and Molecular Biology
Volume 4, Issue 1, January 2019, Pages: 6-16
Received: Mar. 13, 2019; Accepted: Apr. 13, 2019; Published: May 17, 2019
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Nahla El-Sayed El-Ashmawy, Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt
Enas Arafa El-Zamarany, Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt
Hoda Abd El-Kader El-Bahrawy, Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt
Enas Abd El-Moneim Zahran, Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt
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Background: Hepatocellular carcinoma (HCC) is the most common histologic type of primary liver cancer. HCC is the second highest mortality rate out of all major malignant carcinomas worldwide. Objectives: The aims of this study were to establish a rapid and easily handled culture method for sufficient expansion of viable and cytotoxic cytokine-induced killer (CIK) cells against HCC. Also, this study aimed to examine the morphologic, phenotypic, and functional characteristics of CIK cells. Method: Peripheral blood mononuclear cells (PBMCs) were cultured in a preliminary static culture to remove adherent cells. The suspended cells were cultured for 14 days with interferon-γ, human monoclonal anti-CD3 antibody and interleukin‑2. Aliquots of induced PBMCs were harvested weekly to assess informative morphologic and phenotypic features of CIK cells. Mature CIK cells were subjected to functional assays that included the production of TNFα and the cytotoxic effect on HCC cell line, HepG2. Findings: CIK cells could be successfully expanded from all samples with a significant increase in T cells, natural killer cells, and natural killer T cells. TNFα concentration in the culture supernatant was significantly increased. The cytotoxic effect of CIK cells on HepG2 cells was nearly 60% at 40:1, effector: target ratio. Regression analysis was used to predict the CIK: HepG2 ratio required to achieve complete cytotoxicity. Conclusion: This study provides a detailed and simple strategy for culturing effective CIK cells. Mature CIK cells showed a high functional capacity against HCC; which will support the further ongoing practice of immunotherapy integration into different current cancer treatment protocols.
Peripheral Blood Mononuclear Cells, CIK Cells, Natural Killer T Cells, Cytotoxicity, Liver Cancer
To cite this article
Nahla El-Sayed El-Ashmawy, Enas Arafa El-Zamarany, Hoda Abd El-Kader El-Bahrawy, Enas Abd El-Moneim Zahran, Cytokine-Induced Killer Cells as an Adoptive Cellular Immunotherapy Strategy for Hepatocellular Carcinoma, Biochemistry and Molecular Biology. Vol. 4, No. 1, 2019, pp. 6-16. doi: 10.11648/j.bmb.20190401.12
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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