Study Shows How Immunotherapies Work Together to Treat Melanoma

Findings published in a recent issue of Cell from University of Pittsburgh researchers illuminate the way in which immunotherapies work together in activating immune responses in order to treat melanoma.

In the aforementioned study, the targets were immune checkpoints LAG3 and PD1 as they inhibit T-cell activity. PD1 therapy utilizes drugs that stem the interaction of PD1 and PD-L1. During the often-prolonged period of battling cancer, immune checkpoints build up on the surface of the T-cells and become brakes, thereby weakening effect of the T-cells.  

Immune Checkpoint Inhibitors

Although immune checkpoint inhibitors have revolutionized cancer therapy, many patients are unable to respond. Therefore, the next step is to determine how to combine these drugs thus improving their efficacy. Dario Vignali, Ph.D., professor at Pittsburgh University and senior author of two of the papers, emphasized the importance of fully understanding these mechanisms in order to achieve optimum results. The professor further stated that these studies were the first fully in-depth investigation of the response by the immune system when LAG3 and PD1 are blocked.

Treating Melanoma

Relatlimab, that targets PD1, received FDA approval in 2022 in combination with nivolumab to treat metastatic melanoma. According to Professor Vignali, prior to the Pittsburgh University study, the underlying mechanisms were unknown. Findings from the study shed light on why combining therapies targeting both checkpoints will improve results for melanoma patients.

Immune responses of the melanoma patients who were treated with either relatlimab, nivolumab, or both were investigated. Tumor and blood samples were analyzed with improved cancer killing results attributed to the combination therapy compared to treatment with either drug alone.

The Second Study

Lawrence Andrews, Ph.D., led the second study. Genetically modified mice were used in a model of melanoma. Clinical results were reinforced by way of T-cells that were deficient in LAG3 and PD1 checkpoints, which improved survival. The researchers conducted a third study agreeing with the previous observations and providing additional information about PD1 and LAG3’s contribution in exhausting T-cells in various ways.

The three papers provided insight into the function of LAG3 and PD1 and led to opportunities to further development in the clinic.

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Last modified: November 18, 2024