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Immunotherapeutic strategies for treatment of hepatocellular carcinoma with antigen-loaded dendritic cells: in vivo study

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Abstract

Hepatocellular carcinoma (HCC) is one of the major health problems in the world. DCs-based vaccines are a promising immunotherapeutic strategy that aims at the optimal for induction of a specific antitumor immune response and destruction of tumor cells. The present study was conducted to investigate the immunogenic characters of whole tumor lysate-pulsed DCs vaccine and its ability to induce a specific antitumor immune response in HCC mice model. We also evaluate the effectiveness of prophylactic and therapeutic immunization strategies against HCC in mice models. Mice-derived DCs were in vitro loaded with whole tumor lysate prepared from liver tissue of HCC mice and evaluated for expression of surface maturation markers CD83 and CD86. In vivo immunization of mice with whole tumor lysate-pulsed DCs was performed in two strategies; prophylactic (pre-exposure to HCC) and therapeutic (post-exposure to HCC). Effectiveness of both protocols was investigated in terms of histopathological examination of liver sections and measurement of serum levels of immune cytokines interferon-γ (IFN-γ) and interleukin-2 (IL-2). Loading of DCs with whole tumor cell lysate exhibited a significant increase in expression of CD83 and CD86. In vivo administration of prophylactic doses of whole tumor lysate-pulsed DCs in mice before induction of HCC evokes a strong antitumor immune response presented by absence of malignant cells in liver sections and the significant increase in IFN-γ and IL-2. Data herein indicated that prophylactic vaccination with whole tumor lysate-pulsed DCs exhibited an effective antitumor immune response against HCC more than therapeutic protocol.

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Abbreviations

CTLs:

Cytotoxic T-lymphocytes

DCs:

Dendritic cells

GM-CSF:

Granulocyte macrophage colony-stimulating factor

HCC:

Hepatocellular carcinoma

IL-4:

Interleukin-4

IL-2:

Interleukin-2

IFN-γ:

Interferon-γ

PBMN:

Peripheral blood monocytes

TAAs:

Tumor-associated antigens

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmacy, Tanta University, El-Bahr Street, Tanta, El-Gharbiya, 31111, Egypt

    Nahla E. El-Ashmawy, Eman G. Khedr, Hoda A. El-Bahrawy & Ola A. El-Feky

  2. Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt

    Enas A. El-Zamarany

Authors
  1. Nahla E. El-Ashmawy
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  2. Enas A. El-Zamarany
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  3. Eman G. Khedr
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  4. Hoda A. El-Bahrawy
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  5. Ola A. El-Feky
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Correspondence to Ola A. El-Feky.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures involving animals were performed in accordance with institutional guidelines and with the approval of the Research Ethics Committee of Faculty of Pharmacy, Tanta University.

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El-Ashmawy, N.E., El-Zamarany, E.A., Khedr, E.G. et al. Immunotherapeutic strategies for treatment of hepatocellular carcinoma with antigen-loaded dendritic cells: in vivo study. Clin Exp Med 18, 535–546 (2018). https://doi.org/10.1007/s10238-018-0521-6

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  • DOI: https://doi.org/10.1007/s10238-018-0521-6

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