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Title: CAR gene transfer to generate antigen specific regulators
Author: Stavrou, M.
ISNI:       0000 0004 7230 4230
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Adoptive transfer of antigen specific regulatory T (Treg) cells was shown to be beneficial for the suppression of autoimmunity. In this study, we engineered antigen-specific Treg-like cells that recognise mouse MHC-class II molecules. The restricted expression of MHCII to professional antigen presenting cells and to inflammatory sites, allow the employment of MHCII specific Treg for suppression of unwanted immune inflammation. A mouse MHCII-specific Chimeric Antigen Receptor (CAR) was used to redirect the specificity of T cells via retroviral transduction, while Foxp3 gene transfer into purified CD4+ cells leads to the acquisition of a Treg-like phenotype. Incorporation of a suicide mechanism within the engineered Treg-like cells for their in vivo selective deletion will prevent long-term immune suppression. The functionality of the generated CAR and the specificity of responses elicited by CAR bearing T cells were validated in vitro. In preliminary in vivo experiments, intravenous injection of C57BL/6 mice with syngeneic mouse MHCII-specific CD4+ T cells, led to GVHD-like toxicity, while no signs of toxicity were observed when Treg-like cells of the same specificity were transferred alone or in a 1:1 mix with mouse MHCII specific CD4+ T cells. These data suggest the suppressive potential of the engineered Treg-like cells.
Supervisor: Stauss, H. ; Pule, M. ; Shlomchik, W. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available