双唾液酸神经节苷脂单克隆抗体治疗儿童高危和复发/难治性神经母细胞瘤研究进展

Advances in the treatment of high-risk and recurrent or refractory neuroblastoma with disialoganglioside monoclonal antibody

儿童神经母细胞瘤(neuroblastoma,NB)预后异质性极强,高危或复发/难治性 NB 患者长期生存率不足 50%。双唾液酸神经节苷脂抗原(disialoganglioside,GD2)在NB细胞中高表达,但在正常组织中呈限制性表达,因此GD2的单克隆抗体(monoclonal antibody,mAb)疗法已成为高危和复发/难治性NB的特异性靶向治疗方案。GD2 mAb与GD2抗原结合形成抗原-抗体免疫复合物后,通过诱导抗体依赖和补体依赖的双重免疫机制而发挥抗肿瘤作用。GD2 mAb疗法可有效提高高危和复发/难治性NB患者生存率,但应关注不同群体疗程中的不良反应管理,同时积极探索GD2 mAb与化疗联合使用的时机,及与免疫检查点抑制剂程序性死亡受体1/程序性死亡-配体1、^(131)I-间碘苯甲基胍或嵌合抗原受体T细胞联合应用的获益与风险等。现就近年来GD2 mAb治疗儿童高危和复发/难治性NB研究进展作一综述,旨在为临床治疗提供一定参考。

The prognosis of pediatric neuroblastoma(NB) is highly heterogeneous,the long-term survival rate of high-risk or recurrent or refractory NB patients remains less than 50%.Disialoganglioside(GD2) is highly expressed in NB cells,but limited expression in normal tissues.Therefore,GD2 monoclonal antibody(mAb) therapy has become a specific immunotherapy for high-risk and recurrent or refractory NB patients.GD2 mAb binds to GD2 antigen to form immune complex,which plays antitumor effects by inducing antibody-dependent and complement-dependent immune mechanisms.GD2 mAb can significantly improve the survival rate of high-risk and recurrent or refractory NB patients,but attention should be paid to the management of adverse reactions in different groups during treatment.The timing of GD2 mAb combined with chemotherapy,as well as the benefits and risks combined with immune checkpoint inhibitors programmed cell death protein-1/programmed cell death 1 ligand-1,iodine-131-labeled metaiiodo-benzylguanidine or chimeric antigen receptor T cells should be explored.This article reviewed the research progress of GD2 mAb in the treatment of high-risk or recurrent or refractory NB in children in recent years,in order to provide some reference for clinical treatment.