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Cytotoxic effects of gamma delta T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy

Sato, Kiyoshi ; Kimura, Shinya ; Segawa, Hidekazu ; Yokota, Asumi ; Matsumoto, Seiji ; Kuroda, Junya ; Nogawa, Masaki ; Yuasa, Takeshi ; Kiyono, Yasushi ; Wada, Hiromi ; Maekawa, Taira

International journal of cancer, 2005-08, Vol.116 (1), p.94-99 [Periódico revisado por pares]

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  • Título:
    Cytotoxic effects of gamma delta T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy
  • Autor: Sato, Kiyoshi ; Kimura, Shinya ; Segawa, Hidekazu ; Yokota, Asumi ; Matsumoto, Seiji ; Kuroda, Junya ; Nogawa, Masaki ; Yuasa, Takeshi ; Kiyono, Yasushi ; Wada, Hiromi ; Maekawa, Taira
  • É parte de: International journal of cancer, 2005-08, Vol.116 (1), p.94-99
  • Notas: ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Feature-1
    content type line 23
  • Descrição: Nitrogen containing-bisphosphonates (N-BPs), widely used to treat bone diseases, have direct antitumor effects via the inactivation of Ras proteins. In addition to the direct antitumor activities, N-BPs expand gd gamma delta T cells, which exhibit major histocompatibility complex-unrestricted lytic activity. BPs accumulate intermediate metabolites which may be tumor antigens in target cells. The purpose of our study was to clarify the cytotoxicity of gd gamma delta T cells expanded ex vivo by the most potent N-BP, zoledronate (ZOL). Especially, we focused on the importance of pretreatment against target cells also with ZOL; 1 m mu M ZOL plus IL-2 increased the absolute number of gd gamma delta T cells 298-768 fold for 14 days incubation. The small cell lung cancer and fibrosarcoma cell lines pretreated with 5 m mu M ZOL showed a marked increase in sensitivity to lysis by gd gamma delta T cells. While, untreated cell lines were much less sensitive to lysis by gdT cells. Video microscopy clearly demonstrated that gd gamma delta T cells killed target cells pre- treated with ZOL within 3 hr. Pretreatment with 80 m mu g/kg ZOL also significantly enhanced the antitumor activity of gd gamma delta T cells in mice xenografted with SBC-5 cells. These findings show that ZOL significantly stimulated the proliferation of gd gamma delta T cells and that gd gamma delta T cells required pre-treatment with ZOL for cytotoxic activity against target cells.
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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