Abstract
Adoptive transfer of antigen-specific T cells is an attractive means to provide cancer patients with immune cells of a desired specificity and the efficacy of such adoptive transfers has been demonstrated in several clinical trials. Because the T cell receptor is the single specificity-determining molecule in T cell function, adoptive transfer of TCR genes into patient T cells may be used as an alternative approach for the transfer of tumor-specific T cell immunity. On theoretical grounds, TCR gene therapy has two substantial advantages over conventional cellular transfer. First, it circumvents the demanding process of in vitro generation of large numbers of specific immune cells. Second, it allows the use of a set of particularly effective TCR genes in large patient groups. Conversely, TCR gene therapy may be associated with a number of specific problems that are not confronted during classical cellular therapy. Here we review our current understanding of the potential and possible problems of TCR gene therapy, as based on in vitro experiments, mouse model systems and phase I clinical trials. Furthermore, we discuss the prospects of widespread clinical application of this gene therapy approach for the treatment of human cancer.
Keywords: Adoptive therapy, gene therapy, T cell receptor (TCR), T lymphocytes, Major Histocompatibility Complex (MHC), human cancer, antigen-specific, molecule, mouse model systems, immunity
Current Gene Therapy
Title: Prospects and Limitations of T Cell Receptor Gene Therapy
Volume: 11 Issue: 4
Author(s): Annelies Jorritsma, Remko Schotte, Miriam Coccoris, Moniek A. de Witte and Ton N.M. Schumacher
Affiliation:
Keywords: Adoptive therapy, gene therapy, T cell receptor (TCR), T lymphocytes, Major Histocompatibility Complex (MHC), human cancer, antigen-specific, molecule, mouse model systems, immunity
Abstract: Adoptive transfer of antigen-specific T cells is an attractive means to provide cancer patients with immune cells of a desired specificity and the efficacy of such adoptive transfers has been demonstrated in several clinical trials. Because the T cell receptor is the single specificity-determining molecule in T cell function, adoptive transfer of TCR genes into patient T cells may be used as an alternative approach for the transfer of tumor-specific T cell immunity. On theoretical grounds, TCR gene therapy has two substantial advantages over conventional cellular transfer. First, it circumvents the demanding process of in vitro generation of large numbers of specific immune cells. Second, it allows the use of a set of particularly effective TCR genes in large patient groups. Conversely, TCR gene therapy may be associated with a number of specific problems that are not confronted during classical cellular therapy. Here we review our current understanding of the potential and possible problems of TCR gene therapy, as based on in vitro experiments, mouse model systems and phase I clinical trials. Furthermore, we discuss the prospects of widespread clinical application of this gene therapy approach for the treatment of human cancer.
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Jorritsma Annelies, Schotte Remko, Coccoris Miriam, A. de Witte Moniek and N.M. Schumacher Ton, Prospects and Limitations of T Cell Receptor Gene Therapy, Current Gene Therapy 2011; 11 (4) . https://dx.doi.org/10.2174/156652311796150390
DOI https://dx.doi.org/10.2174/156652311796150390 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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