Long-term functionality of TCR-transduced T cells in vivo.
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.
Coccoris
Miriam
M
Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Swart
Erwin
E
de Witte
Moniek A
MA
van Heijst
Jeroen W J
JW
Haanen
John B A G
JB
Schepers
Koen
K
Schumacher
Ton N M
TN
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
D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin