Chen Pengwen, Paraiso West Kristian Dizon, Cabral Horacio
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Red Arrow Therapeutics, Inc, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0003, Japan.
Macromol Biosci. 2023 Dec;23(12):e2300275. doi: 10.1002/mabi.202300275. Epub 2023 Aug 29.
Cytokines can coordinate robust immune responses, holding great promise as therapeutics against infections, autoimmune diseases, and cancers. In cancer treatment, numerous pro-inflammatory cytokines have displayed promising efficacy in preclinical studies. However, their clinical application is hindered by poor pharmacokinetics, significant toxicity and unsatisfactory anticancer efficacy. Thus, while IFN-α and IL-2 are approved for specific cancer treatments, other cytokines still remain subject of intense investigation. To accelerate the application of cytokines as cancer immunotherapeutics, strategies need to be directed to improve their safety and anticancer performance. In this regard, delivery systems could be used to generate innovative therapies by targeting the cytokines or nucleic acids, such as DNA and mRNA, encoding the cytokines to tumor tissues. This review centers on these innovative delivery strategies for cytokines, summarizing key approaches, such as gene delivery and protein delivery, and critically examining their potential and challenges for clinical translation.
细胞因子可以协调强大的免疫反应，作为治疗感染、自身免疫性疾病和癌症的药物具有巨大潜力。在癌症治疗中，许多促炎细胞因子在临床前研究中已显示出有前景的疗效。然而，它们的临床应用受到药代动力学不佳、显著毒性和抗癌疗效不理想的阻碍。因此，虽然干扰素-α和白细胞介素-2已被批准用于特定的癌症治疗，但其他细胞因子仍在深入研究中。为了加速细胞因子作为癌症免疫治疗药物的应用，需要采取策略来提高它们的安全性和抗癌性能。在这方面，递送系统可用于通过将细胞因子或编码细胞因子的核酸（如DNA和mRNA）靶向肿瘤组织来产生创新疗法。本综述聚焦于这些细胞因子的创新递送策略，总结关键方法，如基因递送和蛋白质递送，并批判性地审视它们在临床转化中的潜力和挑战。
