A new study from Moffitt Cancer Center may offer a breakthrough for patients with advanced melanoma who don't respond to current immunotherapy treatments. The research, published in the Journal for ImmunoTherapy of Cancer , found that adding a third immune-targeting drug to existing therapies helped shrink tumors in lab models of treatment-resistant melanoma.
Immunotherapy works by activating the body's own immune system to attack cancer. While these treatments have improved survival for many melanoma patients, a large percentage either don't respond or eventually relapse. Scientists are now searching for new drug combinations to overcome this resistance.
In this study, researchers tested combinations of drugs that block immune checkpoints, molecules like PD-1, LAG-3 and TIM-3 that regulate immune responses. These checkpoints can be hijacked by cancer cells to avoid being destroyed.
Led by Keiran Smalley, Ph.D. , director of Moffitt's Donald A. Adam Melanoma and Skin Cancer Center of Excellence , the research team found that a combination targeting all three checkpoints was especially effective in models that had not responded to standard therapies. The triplet therapy helped restore immune function and led to complete tumor regressions in some cases.
"TIM-3 is often found on immune cells that are too exhausted to fight cancer effectively," said Smalley. "By blocking TIM-3 in addition to PD-1 and LAG-3, we saw a more powerful and targeted immune response, even in difficult-to-treat tumors."
Researchers also analyzed tumor samples from melanoma patients and found that TIM-3 was more common in those who had not responded to immunotherapy. This suggests that targeting TIM-3 could be especially useful as a second-line treatment strategy.
Importantly, the triple-drug combination did not appear to cause increased toxicity, supporting its potential for future clinical trials.
"Our findings offer a new approach to treating melanoma in patients who currently have few options," Smalley said. "We're excited about the potential to bring this strategy to clinical trials and ultimately to patients."
This study was supported by the Florida Bankhead-Coley Research Program (24B04), the National Institutes of Health (P30CA076292, P30CA042014) and the Huntsman Cancer Foundation.
About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 57 National Cancer Institute-designated Comprehensive Cancer Centers , a distinction that recognizes Moffitt's scientific excellence, multidisciplinary research, and robust training and education. Moffitt's expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet®
