Institute of Bioengineering, Lausanne, CH-1015, Switzerland.
Institute of Bioengineering, Lausanne, CH-1015, Switzerland; Institue of Materials Science and Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.
Curr Opin Chem Biol. 2021 Jun;62:43-52. doi: 10.1016/j.cbpa.2021.01.007. Epub 2021 Mar 6.
Cytokines are key modulators of the immune responses and represent promising therapeutics for a variety of cancers. However, successful translation of cytokine-based therapy to the clinic is limited by, among others, severe toxicities and lack of efficacy due to cytokine pleiotropy and off-target activation of cells. Engineering cytokines with enhanced therapeutic properties has emerged as a promising strategy to overcome these challenges. Advances in protein engineering and protein-polymer conjugate technologies have fostered the generation of cytokines with enhanced target cell specificity and longer half-life than the native ones. These novel cytokines exhibit reduced systemic toxicities while focusing the activities at the tumor site, thus, enhancing antitumor immunity. The growing toolbox of cytokine engineering strategies will further stimulate the development of smart cytokine-based immunotherapies with enhanced efficacy and safety profiles.
细胞因子是免疫反应的关键调节剂，是多种癌症有前途的治疗药物。然而，细胞因子疗法在临床上的成功应用受到多种因素的限制，包括由于细胞因子的多效性和对细胞的非靶向激活而导致的严重毒性和疗效缺乏。用增强治疗特性的细胞因子进行工程改造已成为克服这些挑战的一种有前途的策略。蛋白质工程和蛋白质-聚合物缀合技术的进步促进了具有增强的靶细胞特异性和比天然细胞因子更长半衰期的细胞因子的产生。这些新型细胞因子在将活性集中在肿瘤部位的同时，降低了全身毒性，从而增强了抗肿瘤免疫。细胞因子工程策略的不断增长的工具包将进一步刺激开发具有增强的疗效和安全性的智能细胞因子免疫疗法。
