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https://scholarbank.nus.edu.sg/handle/10635/156923
DC Field | Value | |
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dc.title | ENGINEERING T LYMPHOCYTES WITH KNOWN SPECIFICITY AND MODIFIED FUNCTION FOR PERSONALIZED IMMUNE THERAPY | |
dc.contributor.author | CECCARELLO ERICA | |
dc.date.accessioned | 2019-07-23T18:00:37Z | |
dc.date.available | 2019-07-23T18:00:37Z | |
dc.date.issued | 2019-01-25 | |
dc.identifier.citation | CECCARELLO ERICA (2019-01-25). ENGINEERING T LYMPHOCYTES WITH KNOWN SPECIFICITY AND MODIFIED FUNCTION FOR PERSONALIZED IMMUNE THERAPY. ScholarBank@NUS Repository. | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/156923 | |
dc.description.abstract | Adoptive T cell transfer has shown limited efficacy against solid tumours. The increased PD-L1 expression in the tumour microenvironment (TME) might mediate T cell suppression by interaction with PD-1. To produce more efficient T cells, we co-transfected lymphocytes with splicing-modifying Antisense Oligonucleotides (AONs) concurrently with mRNA coding for HBV-specific TCRs. Using AONs targeting perforin or interferon-γ we first demonstrated that it is possible to modify both specificity and function of lymphocytes. We then designed AONs inducing the skipping of the exon coding for the transmembrane domain of PD-1, in order to produce soluble PD-1 to neutralize the PD-L1 in the TME. After transfection, we detected an increased production of soluble PD-1, and the modification improved the efficiency of the engineered lymphocytes in 3D killing assays and in vivo. In conclusion, we improved the effectiveness of TCR-redirected T cells in situ, which could reduce the immunosuppression in the TME. | |
dc.language.iso | en | |
dc.subject | T lymphocytes, Antisense Oligonucleotides, co-electroporation, soluble PD-1, tumor microenvironment, functional modification | |
dc.type | Thesis | |
dc.contributor.department | MICROBIOLOGY & IMMUNOLOGY | |
dc.contributor.supervisor | Qing Feng Chen | |
dc.contributor.supervisor | Antonio Bertoletti | |
dc.description.degree | Ph.D | |
dc.description.degreeconferred | DOCTOR OF PHILOSOPHY (SOM) | |
Appears in Collections: | Ph.D Theses (Open) |
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CeccarelloE.pdf | 3.34 MB | Adobe PDF | OPEN | None | View/Download |
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