A bioengineer remodels cell surfaces to prod the immune system.

Darrell Irvine is focusing his engineer’s mind to boost the body’s defenses against cancer. He’s also working on ways to deliver drugs directly—and only—to the cells that need them.

T cells from the immune system can be removed from a cancer patient, trained in a laboratory dish to recognize and attack tumor cells, and then returned to the patient ready for battle. In some clinical trials, up to 70 percent of patients with advanced melanoma have seen their tumors shrink with this experimental immunotherapy.

These tumor-hunting T cells don’t remain active for long, however, unless the patient receives sustained doses of stimulatory interleukins such as IL-2. These powerful immune stimulants can cause low blood pressure, flu-like symptoms, nausea, diarrhea, and dizziness. For some patients, this adjuvant drug treatment makes T-cell therapy too dangerous.

But what if the T cells could carry their own tiny supplies of interleukins, just enough for their own needs?

HHMI investigator Darrell Irvine has found a way. In his laboratory at the Massachusetts Institute of Technology, he and his colleagues make nanoparticles filled with interleukins and attach these immune “booster kits” to the surface of T cells. They’re so minuscule that 100 booster kits can fit on just 3 percent of the cell’s surface area, where they slowly release their contents to the cell.

By “getting the drug just to the cells that need it,” says Irvine, “we’re looking for the extra nudge that could take immune-cell therapy from working [only] in a subset of people to working in nearly all patients.”

Irvine and postdoctoral research associate Matthias Stephan mounted booster kits containing IL-15 and IL-22 onto T cells extracted from metastatic melanoma tumors implanted under the skin of mice. The T cells were “educated” in laboratory dishes to recognize and destroy the melanoma cells. When infused back into the rodents, the enhanced T cells rapidly proliferated and accurately zeroed in on the metastatic tumors, according to the researchers’ report in the September 2010 Nature Medicine. Importantly, the enhanced cells remained viable longer than untreated T cells and increased the survival rates for the cancer-ridden mice receiving them.

Photo: Matt Kalinowski

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