Mora Jaume
a Department of Pediatric Onco-Hematology and Developmental Tumor Biology Laboratory , Hospital Sant Joan de Déu, Passeig Sant Joan de Déu , Barcelona , Spain.
Expert Rev Clin Pharmacol. 2016;9(5):647-53. doi: 10.1586/17512433.2016.1160775. Epub 2016 Mar 21.
Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood, with 60% of patients presenting with high risk (HR) NB by means of clinical, pathological and biological features. The 5-year survival rate for HR-NB remains below 40%, with the majority of patients suffering relapse from chemorefractory tumor. Immunotherapy is the main strategy against minimal residual disease and clinical experience has mostly focused on monoclonal antibodies (MoAb) against the glycolipid disialoganglioside GD2. Three anti-GD2 antibodies have been tested in the clinic including murine 14G2a, human-mouse chimeric ch14.18 and 3F8. Anti-GD2 MoAb induces cellular cytoxicity against NB and is most effective when effector cells like natural killer cells, granulocytes and macrophages are amplified by cytokines. The combination of cytokines IL-2 and GM-CSF with the anti-GD2 MoAb ch14.18 (Dinutuximab) has shown a significant improvement in outcome for HR-NB. The FDA and EMA approved dinutuximab (Unituxin(R)) in 2015 for the treatment of patients with HR-NB who achieved at least a partial response after multimodality therapy.
神经母细胞瘤（NB）是儿童期最常见的颅外实体瘤，60%的患者根据临床、病理和生物学特征表现为高危（HR）NB。HR-NB的5年生存率仍低于40%，大多数患者会出现化疗难治性肿瘤复发。免疫疗法是针对微小残留病的主要策略，临床经验大多集中在针对糖脂双唾液酸神经节苷脂GD2的单克隆抗体（MoAb）上。三种抗GD2抗体已在临床上进行了测试，包括鼠源性14G2a、人鼠嵌合型ch14.18和3F8。抗GD2 MoAb可诱导针对NB的细胞毒性，当自然杀伤细胞、粒细胞和巨噬细胞等效应细胞通过细胞因子扩增时最为有效。细胞因子IL-2和GM-CSF与抗GD2 MoAb ch14.18（地努图希单抗）联合使用已显示HR-NB的预后有显著改善。美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）于2015年批准地努图希单抗（Unituxin®）用于治疗在多模式治疗后至少获得部分缓解的HR-NB患者。
