Neuroblastoma (NBL) cells highly express disialoganglioside GD2, which is restricted and weakly expressed in selected healthy cells, making it a desirable target of immunotherapy. Over the past two decades, application of dinutuximab, an anti-GD2 monoclonal antibody (mAb), has been one of the few new therapies to substantially improve outcomes to current levels. Given the persistent challenge of relapse and therapeutic resistance, there is an urgent need for new effective and tolerable treatment options for high-risk NBL. Recent breakthroughs in immune checkpoint inhibitor (ICI) therapeutics have not translated into high-risk NBL, like many other major pediatric solid tumors. Given the suppressed tumor microenvironment (TME), single ICIs like anti-CTLA4 and anti-PD1 have not demonstrated significant antitumor response rates. Meanwhile, emerging studies are reporting novel advancements in GD2-based therapies, targeted therapies, nanomedicines, and other immunotherapies such as adoptive transfer of natural killer (NK) cells and chimeric antigen receptors (CARs), and these hold interesting promise for the future of high-risk NBL patient care. Herein, we summarize the current state of the art in NBL therapeutic options and highlight the unique challenges posed by NBL that have limited the successful adoption of immune-modifying therapies. Through this review, we aim to direct the field’s attention to opportunities that may benefit from a combination immunotherapy strategy.
神经母细胞瘤（NBL）细胞高表达双唾液酸神经节苷脂GD2，而该抗原在特定健康细胞中表达受限且微弱，这使其成为理想的免疫治疗靶点。过去二十年间，抗GD2单克隆抗体迪妥昔单抗的应用，是显著提升疗效至当前水平的少数新疗法之一。鉴于复发和治疗耐药性仍是持续存在的挑战，亟需为高危NBL患者开发新型有效且可耐受的治疗方案。尽管免疫检查点抑制剂（ICI）疗法近期取得突破性进展，但与许多其他主要儿童实体瘤类似，其在高危NBL治疗中尚未显现显著疗效。由于肿瘤微环境（TME）处于抑制状态，抗CTLA4、抗PD1等单药ICI疗法未能展现出显著抗肿瘤应答率。与此同时，新兴研究报道了基于GD2的疗法、靶向治疗、纳米药物及其他免疫疗法（如自然杀伤细胞过继转移和嵌合抗原受体疗法）的创新进展，这些为高危NBL患者的未来治疗带来了值得期待的前景。本文系统综述当前NBL治疗领域的最新进展，重点剖析NBL特有的、限制免疫调节疗法成功应用的临床挑战。通过本综述，我们旨在引导该领域关注可能受益于联合免疫治疗策略的发展方向。
Current Knowledge and Perspectives of Immunotherapies for Neuroblastoma
肿瘤(癌症)患者之家