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* Division of Immunology and
Division of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands
To broaden the applicability of adoptive T cell therapy to cancer types for which tumor-specific T cells cannot routinely be isolated, an effort has been made to develop the transfer of tumor-specific TCR genes into autologous T cells as a novel immunotherapeutic approach. Although such TCR-modified T cells have been shown to react to Ag encounter and can be used to break tolerance to defined self-Ags, the persistence and capacity for renewed expansion of TCR-modified T cells has not been analyzed. To establish whether TCR-transduced T cells can provide recipients with long-term Ag-specific immune protection, we analyzed long-term function of TCR transduced T cells in mouse model systems. We demonstrate that polyclonal populations of T cells transduced with a class I restricted OVA-specific TCR are able to persist in vivo and respond upon re-encounter of cognate Ag as assessed by both proliferation and cytolytic capacity. These experiments indicate that TCR gene transfer can be used to generate long-term Ag-specific T cell responses and provide a useful model system to assess the factors that can promote high-level persistence of TCR-modified T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This research was supported by the European Union 6th Framework program (ATTACK).
2 M.C. and E.S. contributed equally to this study.
3 Current address: Laboratory of Tumor Immunology, Department of Medical Oncology, ErasmusMC-Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands.
4 Current address: Institute for Regeneration Medicine, University of California San Francisco, San Francisco, CA 94143.
5 Address correspondence and reprint requests to Prof. Ton N. M. Schumacher, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. E-mail address: t.schumacher{at}nki.nl
6 Abbreviations used in this paper: ACT, adoptive cell transfer; TIL, tumor-infiltrating lymphocyte; WSN-OVA, A/WSN/33-OVA virus; rVV-OVA, recombinant vaccinia virus encoding OVA.
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