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Blood, 1 August 2006, Vol. 108, No. 3, pp. 870-877.
Prepublished online as a Blood First Edition Paper on April 6, 2006; DOI 10.1182/blood-2005-08-009357.
Previous Article | Next Article 
Submitted August 8, 2005
Accepted March 15, 2006
Targeting self antigens through Aalogeneic TCR gene
transfer
Moniek A de Witte, Miriam Coccoris, Monika C Wolkers, Marly D van den Boom, Elly M Mesman, Ji-Ying Song, Martin van der Valk, John B.A.G. Haanen, and Ton N.M. Schumacher*
Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Division of Experimental Animal Pathology, The Netherlands Cancer Institute, Amsterdam
* Corresponding author; email: tschum{at}nki.nl.
Adoptive transfer of T cell receptor genes has been
proposed as an attractive approach for immunotherapy in
cases where the endogenous T cell repertoire is
insufficient. While there is promising data
demonstrating the capacity of TCR-modified T cells to
react to foreign antigen encounter, the feasibility of
targeting tumor-associated self antigens has not been
addressed. Here we demonstrate that T cell receptor gene
transfer allows the induction of defined self antigen-
specific T cell responses, even when the endogenous T
cell repertoire is non-reactive. Furthermore, we show
that adoptive transfer of T cell receptor genes can be
used to induce strong antigen-specific T cell
responsiveness in partially MHC-mismatched hosts without
detectable graft-versus-host disease. These results
demonstrate the feasibility of utilizing a collection
of 'off the shelf' T cell receptor genes to target
defined tumor-associated self antigens and thereby form
a clear incentive to test this immunotherapeutic
approach in a clinical setting.

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