Genetically modified antigen specific NK cells

Aras, Mertkaya (2022) Genetically modified antigen specific NK cells. [Thesis]

Full text not available from this repository. (Request a copy)


cell receptor (TCR) gene therapy can be used to redirect the activity of cytotoxic T cells towards tumor antigens. However, due to the heterodimeric nature of the TCR molecule, TCRα and TCRβ chains introduced by gene delivery have a risk of pairing with the endogenously expressed β or α chains in the T cell. This phenomenon, called mispairing, gives rise to problematic mixed TCR dimers with unpredictable specificity. Our group has previously shown the proof-of-concept for NK cells genetically modified to express functional TCRs (TCR-NK cells) to overcome the mispairing problem. TCR-NK cells expressing CD3δ, CD3γ, CD3ε and TCRα/ß on their cell surface can detect an antigenic peptide presented by MHC-I and selectively show antigen-specific cytotoxic activity. Since NK cells already express CD3ζ, its overexpression in TCR-NK cells does not increase antigen-specific triggering. On the contrary, increased background activity against non-specific targets is observed in TCR-NK cells with CD3ζ overexpression. The underlying mechanism of this effect is yet unknown. IV In this study, we aimed to analyze in detail the gene expression profiles of TCR-NK cells to understand the transcriptomic changes associated with genetic modification. Our results demonstrate that the use of CD3ζ overexpression dramatically effects gene expression profile and might lead to aberrant behavior of TCR-NK cells. We conclude that the inclusion of CD3ζ in vector design may be deleterious to the antigen-specificity of TCR-NK cells. Further development of TCR-NK cells should rely on expression of only CD3δγε components of the CD3 complex
Item Type: Thesis
Uncontrolled Keywords: Cancer Immunotherapy. -- TCR-NK cells. -- RNA sequencing. -- CD3ζ. -- Kanser immunoterapisi. -- TCR-DÖ hücreler. -- RNA dizileme
Subjects: T Technology > TA Engineering (General). Civil engineering (General) > TA164 Bioengineering
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Dila Günay
Date Deposited: 04 Jul 2023 13:58
Last Modified: 04 Jul 2023 13:58

Actions (login required)

View Item
View Item