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TCR Gene Therapy of Spontaneous Prostate Carcinoma Requires In Vivo T Cell Activation¹

Moniek A. de Witte^2,*, Gavin M. Bendle^2,*, Marly D. van den Boom^*, Miriam Coccoris^3,*, Todd D. Schell, Satvir S. Tevethia, Harm van Tinteren, Elly M. Mesman, Ji-Ying Song and Ton N. M. Schumacher^4,*

^* Division of Immunology, Division of Experimental Animal Pathology, and Biometrics Department, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands; and Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033

Analogous to the clinical use of recombinant high-affinity Abs, transfer of TCR genes may be used to create a T cell compartment specific for self-Ags to which the endogenous T cell repertoire is immune tolerant. In this study, we show in a spontaneous prostate carcinoma model that the combination of vaccination with adoptive transfer of small numbers of T cells that are genetically modified with a tumor-specific TCR results in a marked suppression of tumor development, even though both treatments are by themselves without effect. These results demonstrate the value of TCR gene transfer to target otherwise nonimmunogenic tumor-associated self-Ags provided that adoptive transfer occurs under conditions that allow in vivo expansion of the 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 grants from the Dutch Cancer Society (NKI 2003–2860), the European Union Sixth Framework program (ATTACK), the National Cancer Institute of the U.S. National Institutes of Health (CA-25000), the American Cancer Society (Research Scholar Grant 04–059-01-LIB), and the Leukaemia Research Fund (06037).

² M.A.d.W. and G.M.B. contributed equally.

³ Current address: Unit of Medical and Tumor Immunology, Erasmus Medical Center, Groene Hilledijk 301, Rotterdam, The Netherlands.

⁴ Address correspondence and reprint requests to Professor Ton N. M. Schumacher, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. E-mail address: t.schumacher{at}nki.nl

⁵ Abbreviations used in this paper: TAA, tumor-associated Ag; TRAMP, transgenic adenocarcinoma of mouse prostate; PIN, prostatic intraepithelial neoplasia; ACT, adoptive cell therapy; TIL, tumor infiltrating lymphocyte; WT-1, wilms tumor Ag 1; PRAME, Preferentially Expressed Ag of Melanoma.

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