干扰素-抗体偶联物的研究与开发进展

Progress in research & development of interferon-antibody conjugates

干扰素(interferon,IFN)抗肿瘤途径包括:直接肿瘤杀伤效应;免疫激活作用;抑制肿瘤新生血管生成。但IFN半衰期短、系统性毒副作用大等缺点又限制其在临床的应用。通过将IFN与靶向某些肿瘤抗原的抗体偶联,得到的偶联物可使IFN靶向性地集中于某些肿瘤附近,同时降低IFN在机体其他部位的浓度,减少IFN的系统性毒副作用。本文介绍了现有的抗体(抗体片段)-干扰素偶联物,并对其抗肿瘤相关作用机制进行探讨,为IFN及抗体为基础的相关偶联物的开发指明了思路。

Interferon（ IFN） kills tumor through： direct tumor killing,stimulating immune response to tumor cells by activating the immune system and inhibiting tumor angiogenesis. However,its clinical application has been restrained by the deficiencies such as short half-life and severe side effects. IFN-antibody fusion can bring IFN to the vicinity of tumors using tumor specific antibody,while reducing the concentration of IFN in the rest parts of the body. Thus,system toxicity caused by IFN can be significantly lessened. We herein summarized the research and development of preclinical antibody-interferon conjugates and provide new thought on the development of IFN or antibody based fusion proteins.