Gao Wei, Pan Jun, Pan Jianping
Institute of Translational Medicine, Zhejiang University City College, Hangzhou 310015, China.
Institute of Cancer, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Cancers (Basel). 2022 Nov 14;14(22):5592. doi: 10.3390/cancers14225592.
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.
黑色素瘤是皮肤癌中最常见且最严重的恶性肿瘤。尽管近年来越来越多的研究彻底改变了晚期黑色素瘤的系统治疗,但在许多国家,黑色素瘤创新药物的可及性仍然受到极大限制。主要由抗原呈递细胞产生的白细胞介素-12(IL-12)调节免疫反应,并在抗原呈递过程中影响T细胞的分化。然而,IL-12的剂量限制性毒性限制了其临床应用。本综述总结了IL-12在黑色素瘤治疗中的基本生物学功能和毒性,并讨论了IL-12的临床应用,特别是IL-12与免疫检查点抑制剂、细胞因子及其他治疗药物的联合应用。我们还总结了几种有前景的技术方法,如已开发的用于改善IL-12或IL-12编码质粒应用的药代动力学、疗效和安全性的载体。