Beyond Ipilimumab: New Approaches Target the Immunological Synapse

Extract

The March 25 approval of ipilimumab (Yervoy) by the U.S. Food and Drug Administration was a milestone for the embattled field of cancer immunotherapy. 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 effects. “We’re all very excited that ipilimumab has been approved for immunotherapy,” said oncologist Suzanne Topalian, M.D. , at Johns Hopkins University in Baltimore. “But we need to continue to search for other drugs in this class that may have more in the way of anti-cancer effects, and hopefully less in the way of side effects.”