Antitumor Activities of Interleukin-12 in Melanoma

SIMPLE SUMMARY: Immunotherapy has been evolving rapidly in recent years. As a key component of the immune system, cytokines play essential roles not only in immune regulation but also in anti-tumor immunity. In the present review, we summarized the basic biological activities of IL-12 and its application in clinical trials for the therapy of melanoma. We also discussed the combined therapy of IL-12 with immune checkpoint inhibitors, cytokines and other therapeutic drugs in preclinical and clinical studies. The immune-related side effects of IL-12 and promising technological approaches that improve the efficacy and safety of IL-12 or IL-12 encoding vectors in the treatment of melanoma are also discussed. ABSTRACT: Melanoma is the most common and serious malignant tumor among skin cancers. Although more and more studies have revolutionized the systematic treatment of advanced melanoma in recent years, access to innovative drugs for melanoma is still greatly restricted in many countries. IL-12 produced mainly by antigen-presenting cells regulates the immune response and affects the differentiation of T cells in the process of antigen presentation. However, the dose-limited toxicity of IL-12 limits its clinical application. The present review summarizes the basic biological functions and toxicity of IL-12 in the treatment of melanoma and discusses the clinical application of IL-12, especially the combination of IL-12 with immune checkpoint inhibitors, cytokines and other therapeutic drugs. We also summarize several promising technological approaches such as carriers that have been developed to improve the pharmacokinetics, efficacy and safety of IL-12 or IL-12 encoding plasmid application.