Stavrou, M;
(2016)
CAR Gene Transfer to Generate Antigen Specific Regulators.
Doctoral thesis , UCL (University College London).
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Abstract
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | CAR Gene Transfer to Generate Antigen Specific Regulators |
| Event: | University College London |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1503502 |
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