Intraperitoneal administration of a tumor-associated antigen SART3, CD40L, and GM-CSF gene-loaded polyplex micelle elicits a vaccine effect in mouse tumor models

Kouichi Furugaki, Lin Cui, Yumi Kunisawa, Kensuke Osada, Kentaro Shinkai, Masao Tanaka, Kazunori Kataoka, Kenji Nakano

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Polyplex micelles have demonstrated biocompatibility and achieve efficient gene transfection in vivo. Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Intraperitoneally administrated polyplex micelles were predominantly found in the lymph nodes, spleen, and liver. Compared with mock controls, the triple gene vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer cells, of which long-term surviving mice showed complete rejection when rechallenged with CT26 tumors. Moreover, the DNA vaccine inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung tumors in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/ CD8a+ T cells into tumors. Depletion of CD4+ or CD8a + T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype.

    Original languageEnglish
    Article numbere101854
    JournalPloS one
    Volume9
    Issue number7
    DOIs
    Publication statusPublished - Jul 11 2014

    Fingerprint

    granulocyte-macrophage colony-stimulating factor
    CD40 Ligand
    Micelles
    Neoplasm Antigens
    micelles
    Granulocyte-Macrophage Colony-Stimulating Factor
    intraperitoneal injection
    Tumors
    DNA Vaccines
    Vaccines
    Genes
    histocompatibility antigens
    recombinant vaccines
    vaccines
    antigens
    T-cells
    Antigens
    Histocompatibility Antigens
    neoplasms
    mice

    All Science Journal Classification (ASJC) codes

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General

    Cite this

    Intraperitoneal administration of a tumor-associated antigen SART3, CD40L, and GM-CSF gene-loaded polyplex micelle elicits a vaccine effect in mouse tumor models. / Furugaki, Kouichi; Cui, Lin; Kunisawa, Yumi; Osada, Kensuke; Shinkai, Kentaro; Tanaka, Masao; Kataoka, Kazunori; Nakano, Kenji.

    In: PloS one, Vol. 9, No. 7, e101854, 11.07.2014.

    Research output: Contribution to journalArticle

    Furugaki, Kouichi ; Cui, Lin ; Kunisawa, Yumi ; Osada, Kensuke ; Shinkai, Kentaro ; Tanaka, Masao ; Kataoka, Kazunori ; Nakano, Kenji. / Intraperitoneal administration of a tumor-associated antigen SART3, CD40L, and GM-CSF gene-loaded polyplex micelle elicits a vaccine effect in mouse tumor models. In: PloS one. 2014 ; Vol. 9, No. 7.
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    abstract = "Polyplex micelles have demonstrated biocompatibility and achieve efficient gene transfection in vivo. Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Intraperitoneally administrated polyplex micelles were predominantly found in the lymph nodes, spleen, and liver. Compared with mock controls, the triple gene vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer cells, of which long-term surviving mice showed complete rejection when rechallenged with CT26 tumors. Moreover, the DNA vaccine inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung tumors in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/ CD8a+ T cells into tumors. Depletion of CD4+ or CD8a + T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype.",
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