Adjuvant Dendritic Cell-Based Tumour Vaccination for Children With Malignant Brain Tumours

Adjuvant Dendritic Cell-Based Tumour Vaccination for Children With Malignant Brain Tumours
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DOI:
10.1002/pbc.22319
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发表时间:
2010-04-01
影响因子:
3.2
通讯作者:
Van Gool, Stefaan W.
Van Gool, Stefaan W.
中科院分区:
医学3区
文献类型:
--
作者:
Ardon, Hilko;De Vleeschouwer, Steven;Van Gool, Stefaan W.

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背景在成人中已经获得了基于树突状细胞(DC)的恶性脑肿瘤疫苗接种的大量经验。在此,我们重点关注在复发性恶性脑肿瘤儿童中获得的结果。总共45名儿童接种了33个高级别胶质瘤(HGG)、5个成神经管细胞瘤(MB)/原始神经外胚层肿瘤(PNET)、4个室管膜瘤和3个非典型畸胎瘤-横纹肌样肿瘤(ATRT)。产生单核细胞来源的DC,并负载肿瘤裂解物,其用作肿瘤相关抗原的来源。在38例患者中,外周血单个核细胞(PBMC)从白细胞分离术中获得,7例患者从新鲜血液样本中获得,7例HGG患者仍然存活,中位随访(FU)为35.7个月(范围12.1-85.6)中位总生存期(OS)为13.5个月(范围1.4-85.6)所有MB/PNET患者均死亡(中位OS 5.7个月,范围4.3-51.2)1例室管膜瘤患者在随访22.3个月时仍然存活,其他3例患者分别在随访7.7个月时死亡,30.1和31.5个月2例ATRT患者分别在随访34.1和52.6个月时仍存活,第3例患者在随访50.5个月时死亡,未发现严重不良事件。在这项探索性研究中,HGG和ATRT似乎比MB/PNET和室管膜瘤对疫苗接种的反应更好。虽然是初步的,但我们的结果是有希望的,并支持在HGG和ATRT的新治疗方案中进一步测试基于DC的免疫疗法。
Background. A large experience with dendritic cell (DC)-based vaccination for malignant brain tumours has been gained in adults Here we focus on the results obtained in children with relapsed malignant brain tumours Procedure. In total 45 children were vaccinated 33 high grade glioma (HGG), 5 medulloblastoma (MB)/primitive neuro-ectodermal tumour (PNET), 4 ependymoma and 3 atypical teratoid-rhabdoid tumour (ATRT) Autologous, monocyte-derived DC were generated and loaded with tumour lysate, which was used as source of tumour-associated antigens Results. In 38 patients peripheral blood mononuclear cells (PBMC) were obtained from leukapheresis and in 7 patients from fresh blood samples 7 HGG patients are still alive with median follow-up(FU) of 35.7 months (range 12.1-85.6) Median overall survival (OS) was 13.5 months (range 1.4-85.6) All patients with MB/PNET died (median OS 5.7 months, range 4.3-51.2) One patient with ependymoma is still alive at 22.3 months FU The other three patients died at, respectively, 7.7, 30.1 and 31.5 months Two patients with ATRT are still alive at, respectively, 34.1 and 52.6 months FU The third patient died at 50.5 months NO severe adverse events were noticed Conclusions. In this exploratory study, HGG and ATRT seem to respond favourably to vaccination than MB/PNET and ependymoma Although preliminary, our results are promising and support further testing of DC-based immunotherapy in new treatment protocols for HGG and ATRT Pediatr Blood Cancel 2010,54 519-525 (C) 2009 Wiley-Liss, Inc