抗CD47靶向治疗研究现状及应用前景

Achievements and concerns of the CD47 targeted anti-cancer therapy

在肿瘤发生发展过程中,肿瘤细胞逃逸了免疫系统的监视;免疫逃逸机制对于研发新的抗肿瘤治疗方案具有重要的意义。免疫治疗旨在激活患者自身的免疫系统,是肿瘤治疗相关研究的前沿,具有广阔的应用前景。CD47是一种广泛表达的细胞表面分子,肿瘤细胞可能借此"别吃我"信号,逃避了肿瘤免疫;肿瘤干细胞中CD47的表达水平甚至比肿瘤细胞更高。通过使用抗CD47抗体阻断CD47-SIRPα通路,从而介导细胞吞噬作用,能够靶向性杀伤肿瘤细胞。现在多项关于CD47靶向治疗的临床试验正在进行中,包括两种单克隆抗体和一种融合蛋白。然而由于使用动物模型不一,可能高估了这些药物的临床疗效预测。现将CD47抗肿瘤治疗相关研究的背景及潜在问题加以综述,并对该治疗的未来应用前景予以展望。

In cancer development and progression, tumor cells escape from the surveillance of our immune system. Understanding the mechanism behind this phenomenon is crucial in developing new anti-cancer therapies. Immunotherapy, which aims to trigger the immune reaction of the patient＇s own immune system, stands in the spotlight of cancer research and has promising applications. CD47 is ubiquitously expressed in many kinds of cells serving as a ＂do-not-eat-me＂ signal. Cancer cells may take advantage of CD47 overex- pression to escape from immunosurveillance. Cancer stem cells have high expression levels of CD47. Blocking the interaction between CD47 and SIRPα can induce targeted phagocytosis of cancer cells. Several clinical trials on three different kinds of CD47-targeted drugs are ongoing, but the animal models used may have a potential issue in estimating clinical efficacy. The present study aims to review the development and current status of anti-CD47 anti-cancer therapy, raise the concerns on the animal models, and discuss some per- spectives on future clinical applications.