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【medical-news】增强杀伤T细胞功能可治疗皮肤癌
Boosting killer T cells shows promise with skin tumours.
T cells can be engineered to better recognize cancer.
An experimental gene-therapy technique has sent two patients with skin cancer into partial remission. It is the first successful use of gene therapy to treat a cancer.
The method will exist solely in the realm of clinical trials for quite some time, researchers caution. Nevertheless, the study, published online this week in Science1, provides proof-of-principle for a new way to tackle previously intractable tumours.
The technique was used to combat melanoma, a form of skin cancer in which pigmented cells form tumours that are often recognizable as unevenly shaped, rapidly growing moles.
The current treatment involves surgical removal of the tumour, sometimes followed by radiation, chemotherapy and drugs to stimulate the immune system.
But the tumours in some patients do not respond to traditional methods, and so Steven Rosenberg and his team at the National Cancer Institute in Bethesda, Maryland, tried a different approach: they added a gene to the immune system that boosts its ability to recognize cancer.
Two of seventeen patients treated this way demonstrated a dramatic recovery: the treatment shrank their tumours by at least 89% and stopped the spread of cancer into other organs. They have maintained this status for over a year, and have not yet experienced any toxic side effects from the procedure.
Gene therapy could use a few examples of success to clear the air after previous failures. A recent gene-therapy trial that tried to help children with a severe immunodeficiency disease, for example, is thought to have given some of them leukaemia.
Mark Davis, an immunologist at the Stanford Comprehensive Cancer Center in California, says it is possible that the gene-therapy technique used by Rosenberg's group could also pose a cancer risk. When any gene is inserted at random into a cell, he notes, it always has a small chance of accidentally turning on or off another gene, which might make the cell grow out of control. But that risk is worth taking when the patient is already facing a lethal disease, he adds.
Rosenberg agrees. "We're trying to treat cancer," he says. "I think people realize we need to use every tool we have available."
Killer cells
Rosenberg's technique relies on the action of certain T cells, which cruise through the blood stream looking for proteins found on the surface of abnormal cells; they then target and kill offending cells. Rosenberg's group and other researchers had previously found that enriching a patient's T cells in those that are particularly good at recognizing melanomas shrank tumours in half of their subjects, but didn't help the other half.2
His team thought that some unresponsive patients were simply not making enough melanoma-recognizing T cells to begin with. So they isolated the genes that code for melanoma receptors, inserted those genes into T cells isolated from each patient, and then injected the engineered cells back into the patients.
The fact that only two out of the seventeen patients in this trial responded is disappointing, says Davis. The researchers suspect the problem was that their technique did not always alter the T cells in the desired way; they say they have improved their technique in the months since this trial was done, so future remission rates should be higher.
Success story?
Antoni Ribas, director of the Cell and Gene Therapy Core Facility at the University of California, Los Angeles, notes that there may be further hurdles, however.
"There may be melanomas that will never respond to immunotherapy," Ribas says. Not all tumours will present proteins that allow them to be recognized, he explains, or some tumours may evade the fatal signals secreted by T cells. Still, he says, the results are impressive.
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Davis notes that experimental immunotherapy treatments often have spotty success rates. "A lot of hopes have been raised, and those hopes have not been fulfilled," he says.
The technique has so far been clinically studied only in melanoma patients, but Rosenberg's group found that T cells engineered to express a different set of receptors were able to recognize many different cancer cells in a lab dish. "We now have T-cell receptors that can recognize over half of all known cancers," says Rosenberg.
The next step will be to test that recognition in humans. Rosenberg's group has applied for permission to do such studies, and expects to be able to start in the next few months.
基因治疗同癌症的斗争
增强杀伤T细胞功能可治疗皮肤癌
Heidi Ledford
重组T细胞可更好识别癌巢
一个实验性基因治疗技术已将两位皮肤癌患者癌巢缩小。这是头一例成功应用基因治疗技术治疗癌症。
研究者持谨慎态度，告诫大家这种方法只进行了短期临床调查。然而，本周科学杂志在线报道说，这项研究为新方法治疗难治性肿瘤提供了依据。这个技术用于治疗黑色素瘤，后者是一种皮肤癌，色素细胞形成肿瘤，肿瘤细胞形态不规则，增长快速。
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作者:admin@医学,生命科学 2011-02-16 05:16
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