IMMUNE 'BRAKE'
Ipilimumab and tremelimumab are monoclonal antibodies -- targeted immune system proteins that interfere with another immune compound called CTLA-4.
Dr. Jedd Wolchok of Memorial Sloan-Kettering in New York, who led a study for ipilimumab, describes CTLA-4 as a "brake" on immune system cells. "It is what prevents our immune system from becoming hyperactivated," he said.
The idea behind these therapies is to temporarily release this brake in the hope that the immune system will find and destroy the cancer, Wolchok said in an interview.
Because drugs like ipilimumab work differently from chemotherapy, it may take longer to prove they work, he said.
Wolchok's own study illustrates the point. He gave ipilimumab to 155 patients with advanced melanoma. After 12 weeks, 53 of the patients developed new tumors, meaning the cancer had progressed and a sign that the drug had failed.
The researchers continued to follow 26 of the 53 and found that in seven, the new tumors eventually shrank.
"It's very hard for me to convince myself that those folks didn't benefit," Wolchok said.
Other studies of ipilimumab presented this week showed the drug improved overall survival in patients with advanced melanoma to 10 to 13 months, compared with an average of six to nine months on standard therapy.
"With these drugs, there very well may be more delayed effects," Schuchter said.
Gajewski pointed to efforts by GlaxoSmithKline, which is using genetic profiling as a means of predicting who will benefit most from the company's experimental immunotherapy drug MAGE-A3 ASCI for advanced melanoma.
Researchers this week said a study of biopsies of melanoma tumors taken from people before treatment uncovered a common genetic "signature" in those who later responded to MAGE-A3 ASCI.
Gajewski said molecular studies like these, which are costly and labor intensive, may reveal which patients will benefit from new immune-system therapies.
