Sait Sameer, Modak Shakeel
a Department of Pediatrics , Memorial Sloan Kettering Cancer Center , New York , NY , USA.
Expert Rev Anticancer Ther. 2017 Oct;17(10):889-904. doi: 10.1080/14737140.2017.1364995. Epub 2017 Aug 14.
Current therapeutic approaches for high-risk neuroblastoma (HR-NB) include high-dose chemotherapy, surgery and radiotherapy; interventions that are associated with long and short-term toxicities. Effective immunotherapy holds particular promise for improving survival and quality of life by reducing exposure to cytotoxic agents. GD2, a surface glycolipid is the most common target for immunotherapy. Areas covered: We review the status of anti-GD2 immunotherapies currently in clinical use for neuroblastomas and novel GD2-targeted strategies in preclinical development. Expert commentary: Anti-GD2 monoclonal antibodies are associated with improved survival in patients in their first remission and are increasingly being used for chemorefractory and relapsed neuroblastoma. As protein engineering technology has become more accessible, newer antibody constructs are being tested. GD2 is also being targeted by natural killer cells and T-cells. Active immunity can be elicited by anti-GD2 vaccines. The rational combination of currently available and soon-to-emerge immunotherapeutic approaches, and their integration into conventional multimodality therapies will require further investigation to optimize their use for HR-NB.
高危神经母细胞瘤(HR-NB)目前的治疗方法包括大剂量化疗、手术和放疗;这些干预措施会带来长期和短期毒性。有效的免疫疗法有望通过减少细胞毒性药物的使用来提高生存率和生活质量。GD2是一种表面糖脂,是免疫疗法最常见的靶点。涵盖领域:我们综述了目前临床上用于神经母细胞瘤的抗GD2免疫疗法的现状以及临床前开发中的新型GD2靶向策略。专家评论:抗GD2单克隆抗体可提高首次缓解期患者的生存率,并且越来越多地用于化疗难治性和复发性神经母细胞瘤。随着蛋白质工程技术的普及,更新的抗体构建体正在进行测试。自然杀伤细胞和T细胞也以GD2为靶点。抗GD2疫苗可引发主动免疫。目前可用和即将出现的免疫治疗方法的合理组合,以及它们与传统多模态疗法的整合,将需要进一步研究以优化其在HR-NB中的应用。