Queen Mary University of London, William Harvey Research Institute, Bone and Joint Research Unit, Barts and The London Medical School , Charterhouse Square , London EC1M 6BQ, UK.
Expert Opin Drug Deliv. 2014 Jan;11(1):101-10. doi: 10.1517/17425247.2014.863872. Epub 2013 Dec 3.
The use of cytokines as therapeutic agents is important, given their potent biological effects. However, this very potency, coupled with the pleiotropic nature and short half-life of these molecules, has limited their therapeutic use. Strategies to increase the half-life and to decrease toxicity are necessary to allow effective treatment with these molecules.
A number of strategies are used to overcome the natural limitations of cytokines, including PEGylation, encapsulation in liposomes, fusion to targeting peptides or antibodies and latent cytokines. Latent cytokines are engineered using the latency-associated peptide of transforming growth factor-β to produce therapeutic cytokines/peptides that are released only at the site of disease by cleavage with disease-induced matrix metalloproteinases. The principles underlying the latent cytokine technology are described and are compared to other methods of cytokine delivery. The potential of this technology for developing novel therapeutic strategies for the treatment of diseases with an inflammatory-mediated component is discussed.
Methods of therapeutic cytokine delivery are addressed. The latent cytokine technology holds significant advantages over other methods of drug delivery by providing simultaneously increased half-life and localised drug delivery without systemic effects. Cytokines that failed clinical trials should be reassessed using this delivery system.
由于细胞因子具有强大的生物学效应，因此将其用作治疗剂非常重要。然而，这种强大的效力，加上这些分子的多效性和半衰期短，限制了它们的治疗用途。为了使这些分子能够有效治疗，需要增加半衰期和降低毒性的策略。
为了克服细胞因子的天然局限性，人们采用了许多策略，包括聚乙二醇化、脂质体包封、与靶向肽或抗体融合以及潜伏细胞因子。潜伏细胞因子是使用转化生长因子-β的潜伏相关肽进行工程设计的，以产生仅在疾病部位释放的治疗性细胞因子/肽，通过疾病诱导的基质金属蛋白酶切割释放。描述了潜伏细胞因子技术的原理，并将其与其他细胞因子传递方法进行了比较。讨论了该技术在开发具有炎症介导成分的疾病的新型治疗策略方面的潜力。
解决了治疗性细胞因子传递的方法。潜伏细胞因子技术通过提供同时增加的半衰期和局部药物递送而没有全身作用，相对于其他药物递送方法具有显著优势。应该使用这种传递系统重新评估在临床试验中失败的细胞因子。
