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Dual T cell receptor expressing CD8+ T cells with tumor- and self-specificity can inhibit tumor growth without causing severe autoimmunity

Item Type:Article
Title:Dual T cell receptor expressing CD8+ T cells with tumor- and self-specificity can inhibit tumor growth without causing severe autoimmunity
Creators Name:Weinhold, M. and Sommermeyer, D. and Uckert, W. and Blankenstein, T.
Abstract:The engineering of Ag-specific T cells by expression of TCR genes is a convenient method for adoptive T cell immunotherapy. A potential problem is the TCR gene transfer into self-reactive T cells that survived tolerance mechanisms. We have developed an experimental system with T cells that express two TCRs with defined Ag-specificities, one recognizing a tumor-specific Ag (LCMV-gp(33)), the other recognizing a self-Ag in the pancreas (OVA). By using tumor cells expressing high and low amounts of Ag and mice expressing high and low levels of self-Ag in the pancreas (RIP-OVA-Hi and RIP-OVA-Lo), we show that 1) tumor rejection requires high amount of tumor Ag, 2) severe autoimmunity requires high amount of self-Ag, and 3) if Ag expression on tumor cells is sufficient and low in the pancreas, successful adoptive T cell therapy can be obtained in the absence of severe autoimmunity. These results are shown with T cells from dual TCR transgenic mice or T cells that were redirected by TCR gene transfer. Our data demonstrate that the approach of adoptively transferring TCR redirected T cells can be effective without severe side effects, even when high numbers of T cells with self-reactivity were transferred.
Keywords:Autoantigens, Autoimmune Diseases, CD8-Positive T-Lymphocytes, Experimental Melanoma, Growth Inhibitors, Neoplasm Antigens, T-Cell Antigen Receptors, T-Lymphocyte Epitopes, Tumor Cell Line, Animals, Chickens, Mice
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:179
Number:8
Page Range:5534-5542
Date:15 October 2007
Official Publication:http://www.jimmunol.org/cgi/content/abstract/179/8/5534
PubMed:View item in PubMed

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