Australasian Biotechnology,
Volume 8 Number 2, March/April 1998, pp. 99-106
CONFERENCE PAPER
Prostate Cancer Gene Therapy
Russell PJ, Martiniello-Wilks R, Lockett LJ, Brookes DE,
Zandvliet D, Watt F, Molloy PL, Khatri A, and Both GW.
Code Number:AU98019
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Recent developments in molecular biology have
provided the opportunity
for new gene
therapy-based approaches for treating prostate cancer. A range of
approaches are being
taken for different cancer types, with over a hundred clinical
trials of gene therapy for cancer
currently approved in the USA. Three types of approach with
potential application for
prostate cancer have been tested in animal models. Attempts have
been made to "rectify"
mutations contributing to cancers by re-introduction of normal
tumour suppressor genes. In
a number of instances, this has led to induction of apoptotic
cell death with substantial
tumour regression. Several laboratories have introduced genes
into tumour cells, either
ex
vivo or in vivo, to express cytokines and/or immune
costimulatory
molecules, in order to
stimulate the immune system and enhance specific targeting of
cancer cells. This could be of
considerable therapeutic benefit for prostate cancers which are
generally poorly
immunogenic. A further approach, and one which we have been
investigating, is termed
enzymedirected prodrug therapy (EPT). In EPT, a gene encoding an
enzyme foreign to
mammalian cells, eg. Herpesvirus thymidine kinase (HSVTK) or
E. coli purine
nucleoside
phosphorylase (PNP), is introduced into the tumour cells where it
is expressed. The
appropriate prodrug substrate for the enzyme, eg. ganciclovir for
HSVTK or 6-methyl purine
2deoxyriboside for PNP, is given systemically but is only
metabolised to its toxic product at
the tumour site. Using recombinant adenovirus we have delivered
both of these EPT systems
to PC3 prostate cancer cells xenografted in nude mice. Both
systems exhibited strong
suppression of tumour growth and enhanced mouse survival.
Approaches to developing
targeting specificity for these systems and their application to
prostate cancer patients are
discussed.
Copyright 1998 Australian Biotechnology Association Ltd.
