AN ARMY of immune cells that can punch through the defences of tumours has been created by genetic engineering. The method could soon be tested in people.
鈥淚f you have cancer, and you鈥檙e a mouse, then I can cure you,鈥� says Chung Lee of Northwestern University in Illinois. 鈥淥f course, there鈥檚 a big leap between mice and humans. But it seems logical that this strategy would work for people too.鈥�
Most researchers trying to use the immune system to beat cancer focus on boosting the immune response. That can have a dramatic effect. But even if the body produces a vast army of immune cells against a cancer, it can still be foiled. That鈥檚 because many cancers release a slew of protective proteins, including a vital one called transforming growth factor beta. TGF-尾 binds to immune cells and tells them to stop attacking their quarry. It forms an invisible fortress around tumours. 鈥淐ancer鈥檚 best weapon is TGF-尾,鈥� says Lee.
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To breach this fortress, Lee鈥檚 team added a mutated gene for a TGF-尾 receptor to cells from mouse bone marrow. The modified marrow produced immune cells that still bound to TGF-尾 but did not respond to its message to stop attacking.
The altered bone marrow was implanted into mice, which were then injected with cancer cells. Of 10 mice injected with melanoma cells, seven were still alive after six weeks and had few signs of tumours. And all but one of five treated mice given prostate cancer cells were still alive after nine weeks. The untreated animals all died within three or seven weeks respectively, the team report in Cancer Research.
The survival differences are striking, says cancer expert Judah Folkman of Harvard Medical School. 鈥淎 few years ago immunologists would have said there was no way you could get immune cells to see tumours in a sea of TGF-尾,鈥� he says. 鈥淣ow for the first time there鈥檚 a potential for transferring a similar technique to the bedside.鈥�
There is a catch, of course. TGF-尾 is also used by healthy cells to fend off the immune system, so breaching this defence greatly increases the risk of autoimmune diseases 鈥� as indeed happened to some of the mice that survived cancer, Lee reports. But the problem is not insurmountable. A 鈥渟uicide gene鈥� could be added to the marrow cells alongside the altered TGF-尾 receptor, for instance. Then, when the altered cells have done their job, patients could be injected with a substance that triggers the suicide gene and kills them off. Alternatively, all the bone marrow could be destroyed and replaced with unmodified cells from the patient.
The technique is also likely to be expensive, as cells from each patient would have to be extracted, modified and then re-implanted. But Lee thinks it should be work against all cancers. And it could be combined with other immune therapies, or with conventional chemotherapy and surgery, he says. 鈥淲e鈥檒l spend a year doing further studies, and then we鈥檒l aggressively pursue human trials.鈥�