Award details

Virus directed enzyme prodrug therapy (VDEPT) for the treatment of solid tumours. Targeting of carboxypeptidase G2 (CPG2) to the membrane of tumour cells to increase the efficacy of a novel

Reference	B08236
Principal Investigator / Supervisor	Professor Anthony Heagerty
Co-Investigators / Co-Supervisors	Dr Maria Castro
Institution	The University of Manchester
Department	Medical and Human Sciences
Funding type	Research
Value (£)	146,165
Status	Completed
Type	Research Grant
Start date	01/02/1999
End date	01/02/2002
Duration	36 months

Abstract

The effectiveness of current cytotoxic drugs for tumour treatment is limited by their toxic effects to normal tissues and their lack of effects on quiescent cells. Virus directed enzyme prodrug therapy (VDEPT) can potentially overcome these limitations, but current clinical VDEPT systems generate drugs which do not kill quiescent cells and which have limited ability to diffuse and kill non-targeted cells. We aim to develop an improved VDEPT system by targeting the prodrug activating enzyme carboypeptidase G2 (CPG2) to the plasma membrane of tumour cell using a viral vector. Adenovirus vectors will encode CGP2 linked to the plasma membrane glycosyl-phospatidyl inositol anchor. Membrane anchored CPG2 will then metabolise a non-toxic mustard glutamate prodrug to a short lived, highly cyctotoxic, phenol mustard drug capable of killing quiescent cells. The active phenol mustard drug will be generated in the extracellular space within the tumour and should be capable of local diffusion to kill tumour cells not targeted by the viral vector. This proposal will therefore implement a novel strategy to deliver a highly efficient prodrug activating system effectively and specifically to a variety of solid tumours.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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