Protective Capacity of Virus-Specific T Cell Receptor-Transduced CD8 T Cells In Vivo

Abstract

The transfer of T cell receptor (TCR) genes by viral vectors represents a promising technique to generate antigen-specific T cells for adoptive immunotherapy. TCR-transduced T cells specific for infectious pathogens have been described, but their protective function in vivo has not yet been examined. Here, we demonstrate that CD8 T cells transduced with the P14 TCR specific for the gp33 epitope of lymphocytic choriomeningitis virus exhibit protective activities in both viral and bacterial infection models in mice.

Nonlytic Lymphocytes Engineered to Express Virus-Specific T-Cell Receptors Limit HBV Infection by Activating APOBEC3

“…1,2 T cells are, however, also essential for the control of chronic viral infections, and virus-specific TCR-redirected T cells have been shown to recognize viral-infected cells in culture and in animal models. 3 Persistent hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are 2 chronic viral diseases for which virus-specific T-cell therapy has a strong rationale. [4][5][6] Both infections are characterized by defects of antigen-specific T cells, and efficient viral control is associated with T-cell functional recovery.…”

Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection

“…T cells can be engineered to express virus-specific (human CMV [HCMV], EBV, HIV, hepatitis B virus [HBV], hepatitis C virus [HCV], SARS) T cell receptors (TCRs) (2)(3)(4)(5)(6). Virus-specific TCR-redirected T cells have shown protective capacity in animal models (7). In humans, the antiviral efficacy of virus-specific TCR-redirected T cells has not yet been demonstrated, even though adoptive transfer of in vitro-expanded autologous virus-specific T cells has shown remarkable efficacy in EBV and HCMV reactivation occurring in immunocompromised patients (8,9).…”

6. Themenbereich somatische Gentherapie: Translationale und klinische Forschung

“…Diese Untersuchungen wurden zum Teil durch das DFG-Schwerpunktprogramm 1230 (siehe oben) unterstützt. Kieback et al, 2008;Leisegang et al, 2010;Anders et al, 2011;Schmidt et al, 2011;Kofler et al, 2011;Rappl et al, 2012;Spranger et al, 2012;Wilde et al, 2012;Mueller et al, 2012;Maliar et al, 2012;Zhou et al, 2012;Chmielewski et al, 2012Chmielewski et al, , 2013Dössinger et al, 2013;Berdien et al, 2013;Hombach et al, 2013;Krebs et al, 2013;Nauerth et al, Kapitel 6.4). Fragen von konkreter Produktentwicklung oder die eigene Reflexion über die Entwicklung des Feldes rücken dagegen in den Hintergrund; Themen wie die öffentliche Wahrnehmung 69 der Gentherapie in Deutschland oder eine Anwendung des Gentransfers in nicht-therapeutischen Kontexten finden sich nur vereinzelt.…”