A new type of drug decreases the damaging side-effects of a promising but imperfect treatment for cancer, interleukin-2. The drug also boosts the tumor-busting capacity of interleukin-2, holding out promise for patients with certain types of cancer. Interleukin-2 induces the production of powerful immune cells that can attack a tumor, and in patients with malignant melanoma and metastatic renal cell carcinoma produces complete remission in 5-10% of cases. Interleukin-2 is approved as a treatment for these two types of cancers, but can also induce potentially dangerous low blood pressure - often requiring hospitalization in intensive care units and limiting its use.
In experiments on mice, Daniela Salvemini and colleagues (publishing in the June issue of Nature Medicine) found that the new drug, dubbed M4043, reversed interleukin-2 mediated low blood pressure and allowed escalation of the dose of interleukin-2. M4043 also induced remission in 50% of cases in one mouse model of cancer, and substantially decreased growth in a model of renal cell carcinoma. The drug seems to work by counteracting the production of an enzyme, superoxide, that is induced by interleukin-2 and may result in the low blood pressure. The use of M4043 holds out the possibility of safer and more effective use of interleukin-2 in people.
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