Metastatic melanoma is a dreadful type of skin cancer arising due to uncontrolled proliferation of melanocytes. It has very poor prognosis, low 5-year survival rates and until recently there were only handful of treatment options for metastatic melanoma patients. The drugs that were approved for the treatment had low response rates and were associated with severe adverse events. With the introduction of monoclonal antibodies against inhibitory immune checkpoints the treatment landscape for metastatic melanoma has changed dramatically. Ipilimumab, the first monoclonal antibody to be approved for the treatment of metastatic melanoma, showed significant improvements in durable response rates in patients and paved the way for next class of monoclonal antibodies. Nivolumab and pembrolizumab, the anti-PD-1 antibodies that were approved 3-years after the approval of ipilimumab, had decent response rates, low relapse rates and showed manageable safety profile. Antibodies against ligands for PD-1 receptors were then developed to overcome the adverse effects of anti-PD-1 antibodies and combination of monoclonal antibodies (ipilimumab plus nivolumab) was tested to increase the response rates. Additional target receptors that regulate T cell activity were identified on T cells and monoclonal antibodies against potential targets such as TIGIT, TIM-3, and LAG-3 were developed. This chapter discusses the details of monoclonal antibodies used for the treatment of melanoma along with the ones that could be introduced in the near future with emphasis on mechanisms by which antibodies stimulate anti-tumor immune response and the specifics of target molecules of the antibodies.
Keywords: ADCC; CTLA-4; Checkpoints; Co-stimulation; LAG-3; PD-1; T cells; TIGIT; TIM-3.