Abstract：
A lot of hope for high-risk cancers is being pinned on immunotherapy but the evidence in children is lacking due to the rarity and limited efficacy of single-agent approaches. Here, we aim to assess the effectiveness of multimodal therapy comprising a personalized dendritic cell (DC) vaccine in children with relapsed and/or high-risk solid tumors using the N-of-1 approach in real-world scenario. A total of 160 evaluable events occurred in 48 patients during the 4-year follow-up. Overall survival of the cohort was 7.03 years. Disease control after vaccination was achieved in 53.8% patients. Comparative survival analysis showed the beneficial effect of DC vaccine beyond 2 years from initial diagnosis (HR = 0.53, P = .048) or in patients with disease control (HR = 0.16, P = .00053). A trend for synergistic effect with metronomic cyclophosphamide and/or vinblastine was indicated (HR = 0.60 P = .225). A strong synergistic effect was found for immune check-point inhibitors (ICIs) after priming with the DC vaccine (HR = 0.40, P = .0047). In conclusion, the personalized DC vaccine was an effective component in the multimodal individualized treatment. Personalized DC vaccine was effective in less burdened or more indolent diseases with a favorable safety profile and synergized with metronomic and/or immunomodulating agents.
摘要：
免疫疗法寄托了高风险癌症的许多希望，但由于单药方法的稀有性和有限的疗效，儿童缺乏证据。这里,我们的目标是在真实世界中使用N-of-1方法评估包括个性化树突状细胞(DC)疫苗在内的多模式疗法在复发性和/或高风险实体瘤儿童中的有效性.在4年的随访期间，48例患者共发生了160例可评估事件。该队列的总生存期为7.03年。53.8%的患者在接种疫苗后实现了疾病控制。比较生存分析显示DC疫苗在初始诊断后2年（HR=0.53，P=0.048）或疾病控制患者（HR=0.16，P=.00053）的有益效果。显示了节拍环磷酰胺和/或长春碱的协同作用趋势（HR=0.60P=.225）。在用DC疫苗引发后,发现免疫检查点抑制剂(ICI)具有强的协同作用(HR=0.40,P=.0047)。总之,个性化DC疫苗是多模式个体化治疗的有效组成部分。个性化DC疫苗在负担较小或较惰性的疾病中有效,具有良好的安全性,并与节拍和/或免疫调节剂协同作用。
