Engineered immune cells yield "unprecedented" results in early cancer trials

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T-Cell therapy has delivered promising results in early trials involving patients with acute lymphoblastic leukemia

T-Cell therapy has delivered promising results in early trials involving patients with acute lymphoblastic leukemia (Credit: NICHD/J. Lippincott-Schwartz(CC2.0)) View gallery (2 images)

Removing immune cells, training them to attack cancer and then reintroducing them into the body has emerged as a promising approach to overcoming the deadly disease. And researchers are now reporting a significant advance in this area, with one early experiment on advanced blood cancer patients producing "unprecedented" response rates of more than 93 percent.

Harnessing the body's own immune system to fight off cancer has been heralded as the fourth pillar in cancer therapies, joining chemotherapy, radiotherapy and surgical removal. While our immune system kicks itself into action as a virus begins to infect us, cancers are able to elude the predatory cells and continue to multiply and grow.

So scientists are exploring ways to give the immune system the upper hand, through what is known as immunotherapy. One arm of this involves harvesting the body's T cells, which are central to the immune response, and using gene transfer to equip them with potent molecules called chimeric antigen receptors (CARs).

When these CAR T cells are introduced back into the body through a vein, they recognize certain proteins on cancer cells, attach themselves and start to kill them off directly. And because these engineered cells can continue to multiply after being returned to the body, the thinking is that the therapy would not need to be administered on an ongoing basis.

Various research groups have had some success in the lab using this approach, called adoptive immunotherapy. One is developing an injectable biogel loaded with T cells for a more targeted treatment, while another pairs the technique with the other major branch of immunotherapy to double-team the tumors with cancer-attacking antibodies.

But scientists are now reporting some truly impressive results from an ongoing study at Seattle's Fred Hutchinson Cancer Research Center. Beginning in 2013, the trial involved 29 patients with advanced blood cancer – specifically acute lymphoblastic leukemia, in which an overproduction of immature white blood cells crowd the bone marrow and stop the production of normal blood cells. Some of the patients had not responded to other treatments, previously relapsed and were not expected to survive more than a few months.

The group received the experimental immunotherapy and of the 29 patients, 27 experienced sustained remissions. Following their infusions, these patients showed no trace of cancer in their bone marrow.

"This is unprecedented in medicine, to be honest, to get response rates in this range in these very advanced patients," researcher Stanley Riddell said when presenting the findings at the annual meeting of the American Association for the Advancement of Science over the weekend.

Riddell's team is continuing to perfect the engineered CAR T cells in an effort to make them safer and more effective. One dangerous side effect of CAR T-cell therapy is cytokine-release syndrome. As the T cells enter the body they produce chemical messengers called cytokines, which help them carry out their task. But this massive release of cytokines into the bloodstream can cause high fever, drops in blood pressure and also death.

The team managed the risk by giving patients with the highest tumor burdens the lowest doses of T cells, which resulted in no high-burden patients experiencing severe side effects. Before this approach was adopted, however, seven patients experienced cytokine-release syndrome so severe they required intensive care.

Meanwhile, in a separate study concerning patients with non-Hodgkin lymphoma, 19 of 30 to receive the immunotherapy experience partial or complete responses.

While the early numbers are promising, the research has not yet been peer-reviewed and published. And the researchers themselves urge caution. While it has proven effective in these particular circumstances on patients with advanced acute lymphoblastic leukemia, it doesn't represent a blanket approach to curing cancer.

"Much like chemotherapy and radiotherapy, it's not going to be a save-all," says Riddell.

Sources: Fred Hutchinson Cancer Research Center, AAAS

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