Tumor ablation by gene-modified T cells in the absence of autoimmunity.

نویسندگان

  • Leanne X J Wang
  • Jennifer A Westwood
  • Maria Moeller
  • Connie P M Duong
  • Wei-Zen Wei
  • Jordane Malaterre
  • Joseph A Trapani
  • Paul Neeson
  • Mark J Smyth
  • Michael H Kershaw
  • Phillip K Darcy
چکیده

Adoptive immunotherapy involving genetic modification of T cells with antigen-specific, chimeric, single-chain receptors is a promising approach for the treatment of cancer. To determine whether gene-modified T cells could induce antitumor effects without associated autoimmune pathology, we assessed the ability of T cells expressing an anti-Her-2 chimeric receptor to eradicate tumor in Her-2 transgenic mice that express human Her-2 as a self-antigen in brain and mammary tissues. In adoptive transfer studies, we demonstrated significant improvement in the survival of mice bearing Her-2(+) 24JK tumor following administration of anti-Her-2 T cells compared with control T cells. The incorporation of a lymphoablative step prior to adoptive transfer of anti-Her-2 T cells and administration of IL-2 were both found to further enhance survival. The reduction in tumor growth was also correlated with localization of transferred T cells at the tumor site. Furthermore, an antigen-specific recall response could be induced in long-term surviving mice following rechallenge with Her-2(+) tumor. Importantly, antitumor effects were not associated with any autoimmune pathology in normal tissue expressing Her-2 antigen. This study highlights the therapeutic potential of using gene-engineered T cells as a safe and effective treatment of cancer.

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عنوان ژورنال:
  • Cancer research

دوره 70 23  شماره 

صفحات  -

تاریخ انتشار 2010