Gene therapy applied against human illness is in the news again with an apparent spectacular success against head and neck cancer. A combined US-UK research team has reported improvements in 25 out of 30 patients with a novel treatment that involves the use of a genetically engineered virus.
Cancers in the head and neck are notoriously difficult to treat. Common in those who make heavy use of tobacco and alcohol, many tumours are inoperable and about a third of diagnosed patients will die from their illness.
The most recent Irish figures available from the National Irish Cancer Registry in Cork indicate there were 292 new cases of malignant head and neck cancer reported in 1996 and in that year 142 people with these cancers died.
The research, reported in the current issue of Nature Medicine, must therefore provide much encouragement for both doctors and patients. While those involved in the limited human trials must be pleased, they also acknowledged that phase III trials must be conducted and be shown to be successful before the therapy is approved and this is unlikely to come before 2004.
Researchers have long sought the "magic bullet" in cancer treatment, a therapy that could identify and kill off cancerous cells while leaving behind healthy tissue. There has only been limited success, however, with such sophisticated treatments, forcing doctors back to the "slash and burn" approach typified by surgery, chemotherapy and radiation.
Scientists have tried a wide range of therapies in their efforts to find the magic bullet, for example piggybacking toxic chemicals on a protein that could selectively bind itself to a cancer cell and so kill it off. The great problem, however, was that too many other cells, including healthy cells, might bind that same protein causing harmful "collateral damage".
However, as more was learned about the human genome and its supreme complexity, researchers became confident they could find a way to identify unique characteristics found only in cancerous cells. The latest approach uses gene therapy, a treatment based on manipulating the human genetic code.
The new work, by researchers at the University of Texas Anderson Cancer Center, US Oncology, the Royal Marsden Hospital in London and Britain's Imperial Cancer Research Fund, uses this complex approach.
Many cancers take hold when a key cancer-fighting gene, P53, is switched off. Proteins produced by P53 help keep mutations that lead to cancer in check, but when these proteins are no longer available at the correct level, the door is opened to cancerous growth.
The typical gene therapy approach involves finding a way to insert a working copy of an essential gene such as P53 back into the cell. A handy method for doing this is to insert a working human gene into a live but weakened virus and then allow the virus to infect cells and so replace the missing protein. This might sound straightforward, but it is extraordinarily difficult to carry off and recent high-profile failures have not helped the researchers' cause, most notably the death last year in the US of Jesse Gelsinger, who died in a gene therapy experiment that went wrong.
However, the US-UK team used a somewhat different method. They used the same ONYX-15 adenovirus used in the Gelsinger experiments, but knocked out one of the virus's own genes rather than trying to insert a human one.
The modification caused the virus to home in on any cells that did not carry a working copy of the P53 gene, in other words, cancer cells. The virus found these cells, infected them and destroyed them, leaving healthy cells untouched.
The treatment was used on 30 dying patients and the tumours shrank in 25 of them. In 19 patients the growths were reduced by half or more and in eight the tumours disappeared completely and six months on they have not returned. Some of these growths were as large as four inches across.
Dr Stanley Kaye, who supervised some of the ONYX-15 trials at the Beatson Oncology Institute in Glasgow, warned against over optimism. "It wouldn't be appropriate to suggest that the data as it is just now demonstrates this is clearly going to be effective. But it is good enough for us to take the next step."
This next step involves a phase III trial involving 300 patients in Britain and the US. Then there will have to be a long assessment period to determine whether the effect wears off and the tumours return.
The results, however, represent a major fillip for gene therapy research and should allow a renewal of optimism for a magic bullet that will strike down cancers and improve the likelihood of a cure.