Kan immunotherapie naast kanker ook ziekten behandelen?

Kan immunotherapie naast kanker ook ziekten behandelen?

oktober 17, 2019 0 Door admin

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shown promise in animals. Payne says she got the idea for this approach from all the attention successful CAR-Ts were receiving at Penn Medicine. It seemed so simple in retrospect: “You’re like, ‘Why didn’t we think of this earlier?’” she adds. Others had tried to target the antibodies that cause this skin disease before, without success. Payne says she is more optimistic about the engineered T cells she is using, which she calls CAAR-T cells (with an extra “A”), for chimeric autoantibody receptor T cells, because they can make more copies of themselves, so their effects could be long-lasting.

Even decades-old immunotherapies are inspiring present-day work. In Paris, David Klatzmann, an immunologist at Sorbonne University, is experimenting with treating autoimmune disorders with low levels of interleukin-2 (IL-2), an immune-signaling molecule first used to treat cancer in the mid-1980s. Back then, high doses of IL-2 proved effective in a small fraction of metastatic tumors—mainly kidney cancer and melanoma—but caused terrible side effects. Klatzmann’s research suggests low doses may be able to treat a wide range of autoimmune conditions by boosting levels of a type of cell called a regulatory T cell, or Treg, which naturally muzzles the immune response. He uses immunotherapy to suppress the immune system—the opposite of what cancer researchers do.

Klatzmann’s university and two other French institutions hold a patent on low-dose IL-2, and he is hosting a meeting in November with other researchers and pharmaceutical companies who are exploring its potential for a wide range of diseases. He says IL-2 is the only molecule that preferentially activates Tregs, and “there is Treg insufficiency in almost every autoimmune disease and also inflammatory disease,” including atherosclerosis, or the hardening of the arteries. He is now testing his approach in phase II clinical trials for autoimmune illnesses, including lupus, type 1 diabetes and multiple sclerosis.

Jerome Ritz, who runs a cell-manufacturing lab at the Dana-Farber Cancer Institute, says CAR-Ts made with engineered Tregs could also be used against inflammation or in transplant patients to prevent rejection. Stem cell transplants can cure some blood cancers but can also lead to life-threatening graft versus host disease, in which immune cells from the donor attack the recipient. It should be possible to engineer so-called CAR-Tregs to induce tolerance to recipient cells—or even to an entire transplanted organ to prevent rejection, says Ritz, who is also a professor at Harvard Medical School.

Penn Medicine’s Epstein recently engineered T cells in mice to attack cells that produce scar tissue after the heart suffers damage. Known as fibrosis, this scarring initially keeps the heart from rupturing, but it can also impair the organ’s ability to fill with blood and pump efficiently. Epstein’s approach worked in mice, reducing the amount of scar tissue, a study recently published in Nature shows. He hopes to test the method in larger animals.

But some experts remain skeptical. Eric Topol, a cardiologist and executive vice president of the Scripps Research Institute, says he doubts Epstein’s approach will work in humans. “It’s interesting science, but it’s a long way off from having implications for people with heart disease,” Topol says. Many treatments that work in mice do not translate well in people, he notes. And although fibrosis is clearly a problem in heart failure, it is not as clear that targeting fibrotic tissue will help patients. He also worries about the safety of any intervention that might affect the beating of the heart. “If you muck around with it, you could actually engender serious heart-rhythm problems,” he says, “which can be deadly.”

Even if this specific work never pans out, Epstein and others say the larger approach is still valid: learning how to manipulate the immune system to fight cancer has taught researchers information they can now use to fight diseases ranging from infections to arthritis.

Maus agrees: “I think we are definitely in a moment where this kind of science, this kind of potential product—engineered T cells—is transformational. They can be applied in so many different settings and diseases,” she says. But “I think it’s still a little bit early to know whether it’s going to be a commercial product for patients.”

ABOUT THE AUTHOR(S)

Karen Weintraub

    Karen Weintraub is a freelance health and science journalist who writes regularly for the New York Times, STAT and USA Today, among others.

    Credit: Nick Higgins

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