Cancer Gene Therapy Flashcards
Give two examples of suicide gene therapies.
Enzyme –> Prodrug –> Active Product –> Mechanism.
HSV-tk –> GCV/ACV –> GCV/ACV triphosphate –> blocks DNA synthesis
Cytosine deaminase –> 5-Fluorocytosine –> 5-fluorouracil –> Blocks DNA / RNa synthesis.
Give one advantage and one disadvantage of the HSV-tk system.
Very immunogenic - IS alerted to recognition of tumour An so subsequent killing by IS.
Phosphonts can’t be passed from one cell to another so very little bystander effect.
What is an oncolytic virus
Engineered with promoter for crucial viral replication genes functioning only in malignant cells
OR have genetic deficiency complemented by overabundance in malignant cells.
How does T-VEC mediate its effects?
Release of tumour derived Ans, expression of GM-CSF, and virus replication promotes antitumour response - exact mechanism unclear!
(GM-CSF stimulates monocytes to differentiate into mature DCs).
What is the structure of a CAR T cell?
Recognition part of an antibody substituted for a TCR and linked to components required for T cell activation e.g.
LAT - linker for T cell activation
ScFv - single chain variable fragment
ZAP70 - Z-chain associated protein kinase (70kDa)
How can the safety of CAR T cells be improved?
Engineer to express inducible caspase-9. Activated with synthetic chemical inducer of DIMERISATION. Clinical trials show elimination of >95% transgenic T cells within 24H.
