Beyond ipilimumab: new approaches target the immunological synapse.

T he March 25 approval of ipilimumab (Yervoy) by the U.S. Food and Drug Administration was a milestone for the embattled field of cancer immuno-therapy. As the first agent to increase overall survival in a phase III melanoma trial, ipilimumab appeared to vindicate the immune surveillance hypothesis of cancer first proposed in 1957. That hypothesis, which posits that the immune system plays a key role in keeping tumors in check, gave rise to hopes that boosting the immune system could eradicate established tumors. After three decades of almost continual futility in the clinic, ipilimumab is the first clear success: It produces durable, complete responses in a small but consistent proportion of melanoma patients. But ipilimumab ' s objective response rate is only 10% – 15%, and the drug sometimes causes severe immune-related side