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Immunotherapy with TCR-redirected T cells: comparison of TCR-transduced and TCR-engineered hematopoietic stem cell-derived T cells

Item Type:Article
Title:Immunotherapy with TCR-redirected T cells: comparison of TCR-transduced and TCR-engineered hematopoietic stem cell-derived T cells
Creators Name:Stärck, L. and Popp, K. and Pircher, H. and Uckert, W.
Abstract:Redirecting Ag specificity by transfer of TCR genes into PBLs is an attractive method to generate large numbers of cytotoxic T cells for immunotherapy of cancer and viral diseases. However, transferred TCR chains can pair with endogenous TCR chains, resulting in the formation of mispaired TCR dimers and decreased or unspecific reactivity. TCR gene transfer into hematopoietic stem cells (HSCs) is an alternative to create T cells with desired Ag specificity, because in this case expression of endogenous TCR chains is then less likely owing to allelic exclusion. We generated TCR-transduced T cells from peripheral T cells using the lymphocytic choriomeningitis virus-specific P14 TCR. After transfer of the P14 TCR genes into HSCs and subsequent reconstitution of irradiated mice, TCR-engineered HSC-derived T cells were produced. We then compared the Ag-specific T cell populations with P14 TCR-transgenic T cells for their therapeutic efficiency in three in vivo models. In this study, we demonstrate that TCR-transduced T cells and TCR-engineered HSC-derived T cells are comparable in controlling lymphocytic choriomeningitis virus infection in mice and suppress growth of B16 tumor cells expressing the cognate Ag in a comparable manner.
Keywords:Cell Differentiation, Cytokines, Animal Disease Models, Gene Expression, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Immunotherapy, Lymphocytic Choriomeningitis, Lymphocytic Choriomeningitis Virus, Experimental Melanoma, Knockout Mice, T-Cell Antigen Receptors, T-Lymphocytes, Genetic Transduction, Animals, Mice
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:192
Number:1
Page Range:206-213
Date:1 January 2014
Official Publication:https://doi.org/10.4049/jimmunol.1202591
PubMed:View item in PubMed

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