靶向炎性细胞因子的生物制剂及其临床应用

Biologics for targeting inflammatory cytokines and their clinical application

摘要:

细胞因子可介导许多生物学过程并受到机体的严格调节，其调节的失控可引发一系列疾病如自身免疫炎症和肿瘤。在过去的十几年中，一些能够有效调节细胞因子生物学作用的生物制剂如重组抗炎细胞因子、细胞因子受体以及中和性抗体等被广泛应用到由细胞因子失调引起的相关疾病的治疗。尤其是近年来，一些具有创新性的靶向细胞因子的新型生物制剂在不断涌现。文中对近年来国际上靶向炎症细胞因子 (TNF-α、IL-1β、IL-6、IL-17) 的生物制剂的研发和临床应用的相关进展进行了综述，指出其副作用和应用风险，并结合其他学者和自己的研究工作提出减少副作用和风险的途径和方法。利用现代生物技术提高抗细胞因子生物制剂针对炎症或肿瘤组织的特异性，是靶向炎性细胞因子生物制剂未来的重要发展方向。

Abstract:

Inflammatory cytokines can mediate many biological processes and are tightly regulated by the body. Loss of control can trigger a range of diseases such as autoimmune inflammation and cancer. Therefore, a number of biological agents that can effectively regulate the biological effects of inflammatory cytokines such as recombinant anti-inflammatory cytokines, cytokine receptors and neutralizing antibodies have been extensively used in the treatment of related diseases caused by the imbalance of inflammatory cytokines. In recent years, in particular, a number of new innovative biological agents for blocking and regulating cytokine activities are emerging. In this article, we review the recent development and clinical use of the biologics targeting TNF-α, IL-1, IL-6 and IL-17, and point out their inherent limitations and clinical risks. Finally, based on the research findings of our own and other scholars, we suggest some approaches and methods for reducing their side-effects and clinical risk. We consider that using modern biotechnology to improve the tissue specificity to inflammatory site and tumor will be an important development direction of such biologics.