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The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following peroral administration route

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Abstract

Previous studies have shown that there are profuse lymphatic tissues under the intestinal mucous membrane. Moreover, vaccine administered orally can elicit both mucous membrane and system immune response simultaneously, accordingly induce tumor-specific cytotoxic T lymphocyte. As a result, the oral route is constituted the preferred immune route for vaccine delivery theoretically. However, numerous vaccines especially protein/peptide vaccines remain poorly available when administered by this route. Nanoemulsion has been shown as a useful vehicle can be developed to enhance the antitumor immune response against antigens encapsulated in it and it is good for the different administration routes. Of particular interest is whether the protein vaccine following peroral route using nanoemulsion as delivery carrier can induce the same, so much as stronger antitumor immune response to following conventional ways such as subcutaneous (sc.) or not. Hence, in the present study, we encapsulated the MAGE1-HSP70 and SEA complex protein in nanoemulsion as nanovaccine NE (MHS) using magnetic ultrasound method. We then immuned C57BL/6 mice with NE (MHS), MHS alone or NE (-) via po. or sc. route and detected the cellular immunocompetence by using ELISpot assay and LDH release assay. The therapeutic and tumor challenge assay were examined then. The results showed that compared with vaccination with MHS or NE (-), the cellular immune responses against MAGE-1 could be elicited fiercely by vaccination with NE (MHS) nanoemulsion. Furthermore, encapsulating MHS in nanoemulsion could delay tumor growth and defer tumor occurrence of mice challenged with B16-MAGE-1 tumor cells. Especially, the peroral administration of NE (MHS) could induce approximately similar antitumor immune responses to the sc. administration, but the MHS unencapsulated with nanoemulsion via po. could induce significantly weaker antitumor immune responses than that via sc., suggesting nanoemulsion as a promising carrier can exert potent antitumor immunity against antigen encapsulated in it and make the tumor protein vaccine immunizing via po. route feasible and effective. It may have a broad application in tumor protein vaccine.

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Abbreviations

APCs:

Antigen-presenting cells

CTL:

Cytotoxic T lymphocyte

HLA:

Human leukocyte antigen

HPLC:

High performance liquid chromatography

HSP:

Heat shock protein

IFN-γ:

Interferon-γ

MAGE:

Melanoma associated antigen

MHS:

MAGE1-HSP70/SEA complex protein

NE:

Nanoemulsion

NE (-):

Nanoemulsion-encaupulated nothing

NE (MHS):

Nanoemulsion-encaupsulated (MAGE1-HSP70/SEA complex protein)

po.:

Peroral

sc.:

Subcutaneous

SEA:

Staphylococcal enterotoxins A

TEM:

Transmission electron microscopy

TSA:

Tumor-specific antigen

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Acknowledgments

This work was supported by grants from China National Natural Science Foundation (No. 30271464, No. 30700994).

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Authors and Affiliations

  1. State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, Shaanxi Province, China

    Wei Ge, Zeng-Shan Li, Yu-Jing Sun, Pei-Zhen Hu, Yang Huang, Shao-Yan Si, Xiu-Min Zhang & Yan-Fang Sui

  2. Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, Shaanxi Province, China

    Wei Ge, Yuan Li, Shan-Hong Zhang & Xiao-Ming Wang

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  1. Wei Ge
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  2. Yuan Li
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  3. Zeng-Shan Li
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  11. Yan-Fang Sui
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Correspondence to Yan-Fang Sui.

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Ge, W., Li, Y., Li, ZS. et al. The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following peroral administration route. Cancer Immunol Immunother 58, 201–208 (2009). https://doi.org/10.1007/s00262-008-0539-9

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