Nanoparticles Smuggle drugs to Immune Cells

(Ivanhoe Newswire) -- A team of engineers has devised a way to deliver cancer-fighting drugs by smuggling them on the backs of the immune cells sent in to fight the tumor. The drugs reach only their intended targets, greatly reducing the risk to the patient.

The new approach could dramatically improve the success rate of immune-cell therapies, which hold promise for treating many types of cancer, according to senior author Darrell Irvine, associate professor of biological engineering and materials science and engineering and a member of MIT's David H. Koch Institute for Integrative Cancer Research. "What we're looking for is the extra nudge that could take immune-cell therapy from working in a subset of people to working in nearly all patients, and to take us closer to cures of disease rather than slowing progression," Dr. Irvine was quoted as saying.

To perform immune-cell therapy, doctors remove immune cells called T cells from the patient, engineer them to target the tumor, and inject them back into the patient. The T cells then hunt down and destroy tumor cells. Clinical trials are under way for ovarian and prostate cancers, and for melanoma.

Although immune-cell therapy is promising, success has been limited by difficulties in generating enough T cells specific to the cancer and getting those T cells to function properly in the patient.To overcome those obstacles, researchers have tried injecting patients with adjuvant drugs that stimulate T-cell growth and proliferation. One class of drugs that has been tested in clinical trials is interleukins — naturally occurring chemicals that help promote T-cell growth but have severe side effects, including heart and lung failure, when given in large doses.

To avoid toxic side effects, Irvine and his colleagues designed drug-carrying pouches made of fatty membranes that can be attached to sulfur-containing molecules normally found on the T-cell surface.  The researchers injected T cells, each carrying about 100 pouches loaded with the interleukins, into mice with lung and bone marrow tumors. Once the cells reached the tumors, the pouches gradually degraded, releasing the drug over a weeklong period. The drug molecules attached themselves to receptors on the surface of the same cells that carried them, stimulating them to grow and divide.

All of the tumors in the mice treated with T cells carrying the drugs disappeared within 16 days. Those mice survived until the end of the 100-day experiment, while mice that received no treatment died within 25 days, and mice that received either T cells alone or T cells with injections of interleukins died within 75 days.

While he is now focusing on immune-cell therapy, Irvine believes his cell pouches could have other applications, including targeted delivery of chemotherapy agents. "There are lots of people studying nanoparticles for drug delivery, especially in cancer therapy, but the vast majority of nanoparticles injected intravenously go into the liver or the spleen. Less than 5 percent reach the tumor," said Irvine.

With a new way to carry drugs specifically to tumors, scientists may be able to resurrect promising drugs that failed in clinical trials because they were cleared from the bloodstream before they could reach their intended targets, or had to be given in doses so high they had toxic side effects.

SOURCE:  Nature Medicine, August 22, 2010.

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