NTRAC awards UK's first drug R&D grants
phase clinical experiments have been awarded to gene therapy trials
that may herald a breakthrough in intra-abdominal cancer which has
an average survival rate of less than 12 months.
The grants are an attempt to bridge the funding gap that exists between the funding for basic science and clinical infrastructure, and the commercial development of therapeutic products undertaken by the pharmaceutical industry.
As a result, the Department of Health (DH) has made a total of £600,000 (€910,000) available to The National Translational Cancer Research Network (NTRAC) over the next two years to distribute to projects testing gene therapies in early phase trials.
NTRAC has awarded up to £300,000 this year to gene therapy trials run by Professor Nick Lemoine, Director of the Cancer Research UK Clinical Centre and Professor Nicol Keith, at the Centre for Oncology & Applied Pharmacology, Glasgow.
Lemoine will be testing whether gene therapy using a modified virus can have an effect on cancer that has spread to the liver from primary sites in the gastrointestinal tracts. New treatments are needed for these patients as the liver metastases often become resistant to chemotherapy with fewer than five per cent living longer than two years.
Lemoine plans to inject an adenovirus intravenously so that the bloodstream carries it to the malignant deposits in the patients' livers. The adenovirus (VTP-1) will have a crucial gene deleted - the E1A Conserved Region 2 (E1A-CR2). E1A-CR2 is able to knock out a key checkpoint controlling the initial phase of DNA replication (G1-S phase), so that the virus can be carried by the host cell's machinery and make more copies of itself.
This stage is missing in cancer cells, allowing uncontrolled replication. Lemoine believes that the mutant VTP-1 adenovirus will home in on cancer cells that have a matching E1A-CR2 mutation. The cancer cells' own malfunctioning checkpoint will be unable to stop the adenovirus replicating and the virus will grow and kill the cancer cells, leaving normal cells untouched.
keith said: "Cancer cells appear to be totally reliant on the enzyme telomerase for survival, and we have identified the molecular switch they use to turn it on. This has enabled us to develop a novel gene therapy, whereby we attach a molecular copy of this switch to a therapeutic gene and deliver it to the cells. The cancer cells think they are switching on telomerase when in fact they are switching on the therapeutic gene, activating a prodrug killing cancer cells while sparing the normal cells."
"The advantage of using telomerase in gene therapy is that it is active in a broad range of cancers, rather than just one or two. However, bringing any new cancer therapy into the clinic is expensive, and our novel telomerase therapy is no exception."
Gene therapy is a relatively new scientific concept, yet it has seen extensive development in just a few years, and over 3,000 patients have received experimental treatment. It is a potent form of treatment as tiny amounts of therapeutic DNA can produce large amounts of the chemotherapy agent in the tumour cell and it's controllable as its activity can be made highly specific for tumour cells.
Dr Len Seymour, NTRAC's biotherapeutics lead, said that most gene therapy clinical trials were run by companies and hence were largely driven by market forces and by the company's patent protection.
"Scientific advancement tends to be incremental, and it is crucial that we have a means to test important hypotheses without always having an eye on the potential sales figures," he added.
