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Cytokine-Induced Killer Cells as an Adoptive Cellular Immunotherapy Strategy for Hepatocellular Carcinoma

Received: 13 March 2019     Accepted: 13 April 2019     Published: 17 May 2019
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Abstract

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.

Published in Biochemistry and Molecular Biology (Volume 4, Issue 1)
DOI 10.11648/j.bmb.20190401.12
Page(s) 6-16
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

Peripheral Blood Mononuclear Cells, CIK Cells, Natural Killer T Cells, Cytotoxicity, Liver Cancer

References
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Cite This Article
  • APA Style

    Nahla El-Sayed El-Ashmawy, Enas Arafa El-Zamarany, Hoda Abd El-Kader El-Bahrawy, Enas Abd El-Moneim Zahran. (2019). Cytokine-Induced Killer Cells as an Adoptive Cellular Immunotherapy Strategy for Hepatocellular Carcinoma. Biochemistry and Molecular Biology, 4(1), 6-16. https://doi.org/10.11648/j.bmb.20190401.12

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    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. Biochem. Mol. Biol. 2019, 4(1), 6-16. doi: 10.11648/j.bmb.20190401.12

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    AMA Style

    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. Biochem Mol Biol. 2019;4(1):6-16. doi: 10.11648/j.bmb.20190401.12

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  • @article{10.11648/j.bmb.20190401.12,
      author = {Nahla El-Sayed El-Ashmawy and Enas Arafa El-Zamarany and Hoda Abd El-Kader El-Bahrawy and Enas Abd El-Moneim Zahran},
      title = {Cytokine-Induced Killer Cells as an Adoptive Cellular Immunotherapy Strategy for Hepatocellular Carcinoma},
      journal = {Biochemistry and Molecular Biology},
      volume = {4},
      number = {1},
      pages = {6-16},
      doi = {10.11648/j.bmb.20190401.12},
      url = {https://doi.org/10.11648/j.bmb.20190401.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.bmb.20190401.12},
      abstract = {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.},
     year = {2019}
    }
    

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  • TY  - JOUR
    T1  - Cytokine-Induced Killer Cells as an Adoptive Cellular Immunotherapy Strategy for Hepatocellular Carcinoma
    AU  - Nahla El-Sayed El-Ashmawy
    AU  - Enas Arafa El-Zamarany
    AU  - Hoda Abd El-Kader El-Bahrawy
    AU  - Enas Abd El-Moneim Zahran
    Y1  - 2019/05/17
    PY  - 2019
    N1  - https://doi.org/10.11648/j.bmb.20190401.12
    DO  - 10.11648/j.bmb.20190401.12
    T2  - Biochemistry and Molecular Biology
    JF  - Biochemistry and Molecular Biology
    JO  - Biochemistry and Molecular Biology
    SP  - 6
    EP  - 16
    PB  - Science Publishing Group
    SN  - 2575-5048
    UR  - https://doi.org/10.11648/j.bmb.20190401.12
    AB  - 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.
    VL  - 4
    IS  - 1
    ER  - 

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Author Information
  • Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt

  • Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt

  • Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt

  • Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt

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