A once maligned drug's second-life as an immune booster
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Thalidomide — a drug long villified for causing severe birth defects when pregnant women took it to relieve morning sickness — has resurfaced in the last decade as a potential boon for patients with certain bone marrow disorders. A new thalidomide derivative called Revlimid was recently approved by the Food and Drug Administration for the treatment of multiple myeloma (a cancer of plasma cells) and myelodysplastic syndrome (a group of diseases characterized by bone marrow that produces abnormal or insufficient blood cells). Despite the promise of thalidomide and Revlimid, however, scientists still don’t fully understand how these drugs work. Now, new research by Rockefeller University scientists is beginning to shed some light on the subject.
In a paper published in the July 15 issue of the journal Blood, Madhav Dhodapkar, Irene Diamond Associate Professor and head of the Laboratory of Tumor Immunology and Immunotherapy, exposes natural killer T (NKT) cells as a major target of Revlimid. He and his colleagues found that Revlimid appears to work by significantly boosting the function of NKT cells — a class of tumor-attacking white blood cells — by improving the cells’ ability to secrete an immune-boosting protein, interferon-Γ. “Cancer patients seem to have the ability to suppress NKT cell function,” Dhodapkar says. “But Revlimid counteracts this inhibition.”
Prior work by Dhodapkar had shown that a dendritic cell vaccine created in his lab was able to boost NKT cell numbers in cancer patients, but these cells still had some functional defects. “This paper suggests that, with Revlamid, we can manipulate the same kind of cell that the vaccine targets,” Dhodapkar says. “And that suggests that the drug and vaccine together will work a lot better than either approach alone.” He and his colleagues are already planning studies to test these combined therapies. But further down the road, Dhodapkar says, the knowledge that Revlimid can boost immune-cell function could be used to improve other vaccines, too.
