Scientists Hail Cancer
Success As Gene Therapy
Helps Shrink Tumours
By James Meek - Science Correspondent,3604,349243,00.html
Scientists have achieved a significant breakthrough in the struggle to make gene therapy work against cancer by using a genetically engineered virus to shrink and in some cases eliminate tumours.
The success is one of a series of recent coups which have revived faith in genetics-based medicine, which were tainted by the death last year of a US teenager, Jesse Gelsinger, in a gene therapy experiment which went wrong.
In the latest tests, reported in the journal Nature Medicine, British and US patients dying of head and neck cancer were treated with a combination of chemotherapy and the modified virus. In 25 out of 30 patients, the tumours shrank; in 19, they shrank by half or more; in eight, the tumours - some as large as 10cm - disappeared, and did not come back after five months.
David Kirn, formerly head of clinical research at the US biotech firm which developed the virus and who is now based at the Imperial Cancer Research Fund in London, said the patients had been so close to death when they were treated that, although their lives had in some cases been lengthened, none was likely to have been cured.
If the virus was approved for general use and the cancer was caught earlier, he said, it would be different.
"This combination therapy, when moved to treat patients where the cancer is less advanced, could definitely lead to cures," he said.
"I am looking in the long term at coming up with a therapy that, in combination with others, cures patients. This is a very, very exciting step in that direction. It's going to be built on by everybody else out there. It's a landmark in that sense."
In a separate piece in Nature Medicine, W French Anderson, the US scientist who jointly led the first gene therapy experiment on a human being in 1989, wrote: "With all its twists and turns, gene therapy seems to be turning the corner after a very bad year."
Head and neck cancer affects about 500,000 people worldwide per year, mainly heavy smokers and drinkers. Researchers picked it as the target for the engineered virus because the tumours are close to the surface, making it possible to inject the virus directly.
Known as ONYX-15, the virus comes from the same adenovirus family which killed Mr Gelsinger.
Unlike that experiment, where researchers were using the virus to get a "good" copy of a defective human gene into Mr Gelsinger's cells, ONYX-15 has one of its own genes knocked out.
This modification means that the virus zooms in on cancer cells, recognising them because, unlike healthy cells, they lack a working copy of a gene called P53. The virus sneaks into the cells, uses their own machinery to replicate, and then destroys them. Healthy cells are untouched.
Yet used by itself, without chemotherapy, the virus is effective in only 15% of patients.
All now depends on whether gene therapies like ONYX-15 can make it through the next stage of tests, the tough, expensive Phase III trials which determine whether treatments make it to the clinics. The trials will be carried out on 300 patients in Britain and the US but, even if it is deemed a success, it is unlikely to be licensed before 2004.
Other promising gene therapies making their way through the regulatory process are treatments for haemophilia and a rare childhood immune system disease, X-linked SCID.
First trials of a drug against chronic myeloid leukemia, which, while not strictly a gene therapy, relied on scientists' genetic knowledge for its development, have had extraordinary results: 31 out of 31 patients went into remission.
However, 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," he said. "But it is good enough for us to take the next step."
The Cancer Research Campaign
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