A new study 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 tumours 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 Centre 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 tumour 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 tumours.”

Researchers also analysed tumour 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.”

Source: H. Lee Moffitt Cancer Center & Research Institute