Combining the recently-approved BRAF inhibitor Zelboraf with an engineered T cell immunotherapy to treat metastatic melanoma may significantly increase tumor responses and survival in an animal model, according to research out of the University of California at Los Angeles ’s Jonsson Comprehensive Cancer Center.
Animals in the study that received the combination therapy had better tumor responses and lived more than twice as long as those getting the BRAF inhibitor or immunotherapy alone, the study showed. Jonsson Cancer Center researchers hope to launch testing in humans within two years.
In the immunotherapy technique, called adoptive T cell transfer (ACT), lymphocytes are genetically engineered to express a receptor that recognizes melanoma cells, creating an army of immune cells that attack the cancer. The lymphocytes are modified genetically to become specific to the melanoma cells and are injected into the body.
About 50 percent of patients with metastatic melanoma have the BRAF mutation and can be treated with Zelboraf. More than 50 percent of those respond well to the drug, but the responses usually last only a few months. With immunotherapy, fewer patients respond, but the responses are more durable.
“The idea was to target two different aspects of anti-cancer biology, hitting the tumor cells themselves with the BRAF inhibitor and adding in T cells educated to induce a specific anti-tumor immune response,” says Richard Koya, MD, a Jonsson Cancer Center scientist and an assistant professor of surgical oncology, in a press release. “The results we saw in this study were very promising,” he says.
“This is a patient population that we are not able to cure,” Koya says. “With what we have now we are just prolonging their lives. We need to have more options, and we hope this combination therapy proves to be an effective alternative.”
The findings of study appear in the Aug. 15, 2012 issue of Cancer Research.