Strong and sustained effector function of memory- versus naïve-derived T cells upon T-cell receptor RNA transfer: Implications for cellular therapy
Thomas S, Klobuch S, Besold K, Plachter B, Dörrie J, Schaft N, Theobald M, Herr W (2012)
Publication Type: Journal article
Publication year: 2012
Journal
Book Volume: 42
Pages Range: 3442-3453
Journal Issue: 12
Abstract
Current protocols used to select CMV-specific T cells for adoptive immunotherapy focus on virus-specific memory T cells from seropositive donors. However, this strategy is not feasible in patients undergoing allogeneic haematopoietic stem-cell transplantation (HSCT) from CMV-seronegative donors. Here, we redirected T cells of CMV-seronegative donors with a human genetically engineered TCR recognizing an HLA-A*0201-binding peptide epitope of CMVpp65. To facilitate clinical translation of this approach, we used a non-viral expression system based on in vitro transcribed RNA and electroporation. Although memory and naïve-derived T-cell subsets were both efficiently transfected by TCR-RNA, memory-derived T cells showed much stronger levels of HLA-A*0201-restricted cytolytic activity to CMV-infected fibroblasts and maintained acquired function for 5-10 days. In addition to redirection of CD8+ cytotoxic T cells, TCR-RNA transfection was capable of redirecting CD4+ T cells into potent Ag-specific Th cells that efficiently triggered maturation of DCs. Our data suggest that memory rather than naïve-derived T cells are the preferred subset for transient TCR expression by RNA electroporation, providing more efficient and sustained virus-specific CD4+ and CD8+ T-cell function. CMV TCR-RNA may represent a suitable therapeutic 'off-the-shelf' reagent to be used in severe CMV infections of HSCT patients when endogenous CMV-specific T-cell immunity is insufficient. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Germany (DE)How to cite
APA:
Thomas, S., Klobuch, S., Besold, K., Plachter, B., Dörrie, J., Schaft, N.,... Herr, W. (2012). Strong and sustained effector function of memory- versus naïve-derived T cells upon T-cell receptor RNA transfer: Implications for cellular therapy. European Journal of Immunology, 42(12), 3442-3453. https://doi.org/10.1002/eji.201242666
MLA:
Thomas, Simone, et al. "Strong and sustained effector function of memory- versus naïve-derived T cells upon T-cell receptor RNA transfer: Implications for cellular therapy." European Journal of Immunology 42.12 (2012): 3442-3453.
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