Abstract：
Therapy for high-risk neuroblastoma (HR NBL) is comprised of multimodal therapy including chemotherapy, surgery, radiation therapy, myeloablative therapy followed by autologous hematopoietic stem cell transplant, and immunotherapy. GD2 is a disialoganglioside that is highly expressed on the surface of neuroblastoma cells, with limited expression on normal tissues, which makes it an attractive target for immunologic therapy. The combination of immunotherapy with murine and chimeric anti-GD2 antibody formulations has improved outcomes compared with standard therapy in HR NBL patients. Naxitamab (Danyelza), a fully humanized anti-GD2 antibody, was developed at Memorial Sloan Kettering Cancer Center (MSKCC) to mitigate adverse reactions related to intolerance of foreign murine and chimeric antigens. Phase I and II studies demonstrating the tolerability and efficacy of naxitamab in patients with relapsed/refractory (r/r) HR NBL prompted its approval by the U.S. Food and Drug Administration (FDA) in 2020 for HR NBL with bone or bone marrow involvement. Initial outcomes with naxitamab are encouraging; however, future trials to maximize drug tolerance and elucidate its optimal role in neuroblastoma therapy in conjunction with other treatment strategies are needed. This review discusses the use of naxitamab in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of r/r HR NBL.
摘要：
高危神经母细胞瘤（HRNBL）的治疗包括多模式治疗，包括化疗，手术,放射治疗,清髓治疗，然后自体造血干细胞移植，和免疫疗法。GD2是一种二唾液酸神经节苷脂，在神经母细胞瘤细胞表面高表达，在正常组织上表达有限，这使得它成为免疫疗法的一个有吸引力的靶点。免疫疗法与鼠和嵌合抗GD2抗体制剂的组合在HRNBL患者中与标准疗法相比具有改善的结果。Naxitamab(Danyelza),完全人源化的抗GD2抗体,是在纪念斯隆·凯特琳癌症中心（MSKCC）开发的，以减轻与外来鼠和嵌合抗原不耐受有关的不良反应。I期和II期研究证明了纳西他单抗在复发/难治性（r/r）HRNBL患者中的耐受性和有效性，促使美国食品和药物管理局（FDA）于2020年批准了具有骨或骨髓受累的HRNBL。纳西他单抗的初步结果令人鼓舞；然而，需要进行未来的试验,以最大限度地提高药物耐受性,并阐明其在神经母细胞瘤治疗中的最佳作用,以及其他治疗策略.本文讨论了纳西他单抗联合粒细胞-巨噬细胞集落刺激因子（GM-CSF）治疗r/rHRNBL的应用。
