Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zurich), Vladimir-Prelog Weg 1-5/10, Zurich CH-8093, Switzerland.
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zurich), Vladimir-Prelog Weg 1-5/10, Zurich CH-8093, Switzerland.
Adv Drug Deliv Rev. 2019 Feb 15;141:67-91. doi: 10.1016/j.addr.2018.09.002. Epub 2018 Sep 7.
Cytokines have long been used for therapeutic applications in cancer patients. Substantial side effects and unfavorable pharmacokinetics limit their application and may prevent dose escalation to therapeutically active regimens. Antibody-cytokine fusion proteins (often referred to as immunocytokines) may help localize immunomodulatory cytokine payloads to the tumor, thereby activating anticancer immune responses. A variety of formats (e.g., intact IgGs or antibody fragments), molecular targets (e.g., extracellular matrix components and cell membrane antigens) and cytokine payloads have been considered for the development of this novel class of biopharmaceuticals. This review presents the basic concepts on the design and engineering of immunocytokines, reviews their potential limitations, points out emerging opportunities and summarizes key features of preclinical and clinical-stage products.
细胞因子在癌症患者的治疗应用中已有很长的历史。大量的副作用和不良的药代动力学限制了它们的应用，并且可能阻止剂量增加到治疗有效的方案。抗体-细胞因子融合蛋白（通常称为免疫细胞因子）可以帮助将免疫调节细胞因子有效载荷定位到肿瘤，从而激活抗癌免疫反应。为了开发这种新型生物制药，已经考虑了多种形式（例如完整的 IgG 或抗体片段）、分子靶标（例如细胞外基质成分和细胞膜抗原）和细胞因子有效载荷。本文介绍了免疫细胞因子设计和工程的基本概念，回顾了它们的潜在局限性，指出了新的机会，并总结了临床前和临床阶段产品的关键特征。
