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Stanford University School of Medicine

Souped-up super-version of IL-2 offers promise in cancer treatment

My sainted grandma was big on chicken soup. For colds, for fevers, for aches and pains. For the blues. “It couldn’t hurt,” she used to say.

But chicken soup, however super, never cured cancer. Interleukin-2, or IL-2, a naturally occurring, hormone-like rabble-rouser of a protein, does.

IL-2, which now can be produced through biotechnology and packaged in vials as a drug, is powerful enough to stop speeding bullets such as advanced metastatic melanoma and kidney cancer. Approved for both of those indications, IL-2 has actually cured about 7 percentof the patients in whom it's been used. That cure rate may sound small, but it's actually very impressive considering that at such advanced stages of cancer virtually all treatments fail.

IL-2 is a master regulator of the immune system. Among other things, it activates a class of cells called T cells that can recognize and mount attacks against tumors. As a drug, however, IL-2 is limited by its tendency to cause severe, dose-limiting side effects such as pulmonary edema, or accumulation of fluid in the lungs due to leakage from the copious capillaries permeating that organ.

In a new study published in Nature, Stanford molecular and cellular physiologist and structural biologist Chris Garcia, PhD, and his teammates have created a mutant version of the protein, which Garcia has dubbed Super-2. As I wrote in my release about this study:

This souped-up form of the protein was several times as potent as the naturally occurring form of IL-2 at slowing tumor growth, as measured by assays employing three different tumor types in culture. But Super-2 is no more proficient than natural IL-2 at activating the immune cell type responsible for causing capillary leakage and the ensuing pulmonary edema.

These lab-induced modifications of IL-2's structure may tilt the drug's benefit-to-risk ratio, allowing its use at lower doses and in an expanded range of indications. As my grandma might have said, "It couldn't hurt."

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