Enhance the anti-tumor action of the immune system by helping it on several fronts. This is the strategy used by the combination of drugs – relatlimab and nivolumab – which act on two different pathways, both involved in the body’s immune response, unlocking mechanisms that the tumor contributes to not making it work effectively. The mix was tested in patients with previously untreated metastatic or unresectable melanoma and compared with nivolumab alone, demonstrating to increase progression-free survival, the time that elapses before the disease progresses. The data emerge from the Relativity-047 study and are the first to involve an anti-LAG-3 antibody.
Relatlimab is in fact an antibody that acts on the gene 3 for the activation of lymphocytes (LAG-3), a surface molecule expressed on effector and regulatory T cells (Treg). LAG-3 regulates the pathway of an inhibitory-type immune checkpoint that limits the activity of T cells, resulting in impaired ability to attack tumor cells. In situations of chronic persistence of diseases such as cancer, T cells manifest progressive functional exhaustion characterized by an upregulation of inhibitory immune checkpoints such as PD-1 and LAG-3. Although LAG-3 and PD-1 are distinct immune checkpoint pathways, they can potentially act synergistically on effector T cells leading to functional depletion of T cells. Relatlimab is an antibody that binds to LAG-3 on T cells, restoring the effector function of depleted T cells. Relatlimab, in combination with nivolumab, is the first anti-LAG-3 antibody to demonstrate a benefit for patients.
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when the cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has steadily increased over the past 30 years. In the United States, it is estimated that in 2021 there will be 106,110 new diagnoses of melanoma and about 7,180 related deaths. Globally, the World Health Organization estimates that, by 2035, the incidence of melanoma will reach 424,102, with 94,308 related deaths. Melanoma is for the most part treatable when treated in the early stages; however, survival rates decrease if regional lymph nodes are involved.