Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Pelotonia Institute for Immune-Oncology, The Ohio State University, Columbus, OH, USA.
Expert Opin Drug Deliv. 2023 May;20(5):579-595. doi: 10.1080/17425247.2023.2208344. Epub 2023 May 3.
Cytokine immunotherapy is a growing field for the treatment of cancer, infectious disease, autoimmunity, and other ailments. Therapeutic cytokines are a class of secreted, small proteins that play a pivotal role in regulating the innate and adaptive immune system by provoking or mitigating immune responses. In the clinic, cytokines are frequently combined with other treatments, such as small molecules and monoclonal antibodies. However, the clinical translation of cytokine therapies is hindered by their short half-life, pleiotropic nature, and off-target effects, which cause diminished efficacy and severe systemic toxicity. Such toxicity limits dosage, thus resulting in suboptimal doses. Accordingly, numerous efforts have been devoted to exploring strategies to promote cytokine therapies by improving their tissue specificity and pharmacokinetics.
Preclinical and clinical research into bioengineering and delivery strategies for cytokines, consisting of bioconjugation, fusion proteins, nanoparticles, and scaffold-based systems.
These approaches pave the way for the development of next-generation cytokine treatments with greater clinical benefit and reduced toxicity, circumventing such issues currently associated with cytokine therapy.
细胞因子免疫疗法是治疗癌症、传染病、自身免疫性疾病和其他疾病的一个新兴领域。治疗性细胞因子是一类分泌的小蛋白，通过引发或减轻免疫反应，在调节先天和适应性免疫系统方面发挥着关键作用。在临床上，细胞因子经常与小分子和单克隆抗体等其他治疗方法联合使用。然而，细胞因子疗法的临床转化受到其半衰期短、多效性和脱靶效应的阻碍，这导致疗效降低和严重的全身毒性。这种毒性限制了剂量，从而导致剂量不足。因此，人们已经做出了许多努力来探索通过提高细胞因子的组织特异性和药代动力学来促进细胞因子疗法的策略。
细胞因子的生物工程和传递策略的临床前和临床研究，包括生物缀合、融合蛋白、纳米颗粒和基于支架的系统。
这些方法为开发具有更大临床效益和降低毒性的下一代细胞因子治疗方法铺平了道路，避免了目前与细胞因子治疗相关的问题。
