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

LXJ Wang, JA Westwood, M Moeller, CPM Duong… - Cancer research, 2010 - AACR
LXJ Wang, JA Westwood, M Moeller, CPM Duong, WZ Wei, J Malaterre, JA Trapani
Cancer research, 2010AACR
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 …
Abstract
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. Cancer Res; 70(23); 9591–8. ©2010 AACR.
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