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A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer

Item Type:Article
Title:A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer
Creators Name:Kieback, E. and Charo, J. and Sommermeyer, D. and Blankenstein, T. and Uckert, W.
Abstract:By transfer of T cell receptor (TCR) genes, antigen specificity of T cells can be redirected to target any antigen. Adoptive transfer of TCR-redirected T cells into patients has shown promising results. However, this immunotherapy bears the risk of autoreactive side effects if the TCR recognizes antigens on self-tissue. Here, we introduce a safeguard based on a TCR-intrinsic depletion mechanism to eliminate autoreactive TCR-redirected T cells in vivo. By the introduction of a 10-aa tag of the human c-myc protein into murine (OT-I, P14) and human (gp100) TCR sequences, we were able to deplete T cells that were transduced with these myc-tagged TCRs with a tag-specific antibody in vitro. T cells transduced with the modified TCR maintained equal properties compared with cells transduced with the wild-type receptor concerning antigen binding and effector function. More importantly, therapeutic in vivo depletion of adoptively transferred T cells rescued mice showing severe signs of autoimmune insulitis from lethal diabetes. This safeguard allows termination of adoptive therapy in case of severe side effects.
Keywords:Adoptive T Cell Therapy, Antibody Depletion, Myc-Tag, Suicide, TCR, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:105
Number:2
Page Range:623-628
Date:15 January 2008
Additional Information:Copyright (c) 2008 by The National Academy of Sciences of the USA
Official Publication:https://doi.org/10.1073/pnas.0710198105
PubMed:View item in PubMed

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