Immune System Humanized Mice: Enabling a New Frontier in Drug Discovery

The past decade has seen remarkable progress in Immuno-oncology; leading to a series of blockbuster new drugs for the treatment of stage IV melanoma. In 2011, the FDA approved a new treatment called Yervoy®, released by Bristol Myers Squibb, which targets one such counter-measure, the immune checkpoint blockade molecule called CTLA-4. In a recent follow up report on the first patients treated with Yervoy®, the clinicians reported 20-30% of patients treated responded with partial or complete responses, with extended lifespan of a median 14 months, and five year survival rates at about 20%. 14 of 15 "complete responders" are going on 54+ and 99+ months post treatment without recurrence. The clinical success was so remarkable that the FDA rushed approval of Yervoy® for this previously untreatable condition. This image is taken from the first publication describing the clinical findings, and shows a patient with intractable stage IV melanoma. At 72 weeks post treatment with Yervoy®, the superficial skin tumors are completely resolved and the patient is without disease. The clinicians in charge of following the first group of patients treated with the drug describe this treatment as "potentially curative"; a language choice rarely used in the oncology setting. This September, Merck won approval for Keytruda® another immuno-oncology drug aimed at the molecule PD-1, which has garnered similar success profiles in patients that did not respond to Yervoy® treatment. Importantly Keytruda® recently won blockbuster designation by the FDA for a second indication, non-small cell lung cancer.