Boosting Melanoma Immunity with Sequential IL-2 and IL-12 Gene Delivery

Melanoma is an aggressive and potentially deadly form of skin cancer that often resists standard treatments. Recent advances in immunotherapy—using the body’s own immune system to fight cancer—have improved outcomes for some patients. However, many people with melanoma still do not respond well to these treatments, and new strategies are needed to help the immune system recognize and eliminate cancer cells more effectively. Interleukin-12 (IL-12) and interleukin-2 (IL-2) are well-established therapies in melanoma treatment, known for their ability to stimulate immune cells. IL-12 works by “training” immune cells to spot and attack cancer cells, while IL-2 encourages these cells to multiply, strengthening the body’s defenses. This project aims to improve on these therapies by delivering IL-12, IL-2, and an additional immune-boosting molecule, 4-1BBL, directly into the tumor in a precise sequence to maximize their effects. Using specially designed nanoparticles—tiny carriers made from safe, biodegradable materials—this approach targets the immune environment within the tumor, aiming to create a stronger and more lasting anti-cancer response.

Our study will investigate how this unique delivery strategy affects the tumor’s immune environment in three ways. First, we will measure how well this method activates immune cells within the tumor, analyzing how this treatment strategy enhances immune cell activation and persistence. Second, we will examine the immune signals within the tumor to see how this approach shapes a supportive anti-cancer environment, including both helpful and suppressive signals. Finally, we will test if this strategy generates a broader immune response by analyzing immune cells in the blood and spleen, which could help prevent the cancer from spreading or returning. Through this research, we aim to understand a new strategy to improve melanoma treatment, maximizing the immune system’s ability to fight melanoma and provide lasting protection.