title: Long-term functionality of TCR-transduced T cells in vivo.
abstract: 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.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: Coccoris
authors.forename: Erwin
authors.initials: E
authors.lastname: Swart
authors.forename: Moniek A
authors.initials: MA
authors.lastname: de Witte
authors.forename: Jeroen W J
authors.initials: JW
authors.lastname: van Heijst
authors.forename: John B A G
authors.initials: JB
authors.lastname: Haanen
authors.forename: Koen
authors.initials: K
authors.lastname: Schepers
authors.forename: Ton N M
authors.initials: TN
authors.lastname: Schumacher
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D018014:Gene Transfer Techniques; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic
chemical_list: D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin