Once, Twice, Three Times a Finding: Reproducibility of Dendritic Cell Vaccine Trials Targeting Cytomegalovirus in Glioblastoma.
Once, Twice, Three Times a Finding: Reproducibility of Dendritic Cell Vaccine Trials Targeting Cytomegalovirus in Glioblastoma.
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DOI：
10.1158/1078-0432.ccr-20-1082
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发表时间：
2020-10-15
影响因子：
11.5
通讯作者：
Sampson, John H.
中科院分区：
文献类型：
--
作者：
Batich, Kristen A.;Mitchell, Duane A.;Healy, Patrick;Herndon, James E., II;Sampson, John H.
尽管胶质母细胞瘤（GBM）的护理标准，包括总切除术，高剂量放疗和剂量限制化疗，这种肿瘤仍然是最具侵略性和治疗挑战性的肿瘤之一。与临床试验中更常见的实体瘤相比，这种诊断的患者数量相对较少，因此新的GBM疗法需要在小型、动力不足、非随机化的环境中进行测试。在2005年至2015年期间确定的约200项注册GBM试验中，近一半是单组研究，样本量不超过50例患者。这些限制使得证明新疗法在GBM和其他罕见和侵袭性癌症中的疗效变得困难。治疗GBM的新型免疫疗法，例如用树突状细胞（DC）接种疫苗，在临床试验中产生了好坏参半的结果。为了解决数量有限的问题，我们在新诊断的GBM患者中使用巨细胞病毒（CMV）特异性DC疫苗连续进行了三项独立的临床试验，其中每个随访研究的样本量几乎增加了一倍。来自第一个盲法随机II期临床试验（NCT 00639639）的随访数据显示，该队列中近三分之一的患者在诊断后五年内没有肿瘤复发。第二项临床试验（NCT 00639639）在诊断后5年的生存率为36%。第一个两组试验（NCT 00639639）的结果显示DC疫苗向引流淋巴结的迁移增加，并且这种迁移增加已在我们更大的确证性临床研究（NCT 02366728）中重现。我们现在已经观察到，接受CMV特异性DC疫苗的GBM研究患者人群中有近三分之一的人获得了特殊的长期存活。
Despite standard of care for glioblastoma (GBM), including gross total resection, high dose radiation, and dose-limited chemotherapy, this tumor remains one of the most aggressive and therapeutically challenging. The relatively small number of patients with this diagnosis compared to more common solid tumors in clinical trials commits new GBM therapies to testing in small, underpowered, non-randomized settings. Among ~200 registered GBM trials identified between 2005 and 2015, nearly half were single-arm studies with sample sizes not exceeding 50 patients. These constraints have made demonstrating efficacy for novel therapies difficult in GBM and other rare and aggressive cancers. Novel immunotherapies for GBM such as vaccination with dendritic cells (DCs) have yielded mixed results in clinical trials. To address limited numbers, we sequentially conducted three separate clinical trials utilizing Cytomegalovirus (CMV) specific DC vaccines in patients with newly diagnosed GBM whereby each follow-up study had nearly doubled in sample size. Follow-up data from the first blinded, randomized phase II clinical trial (NCT00639639) revealed that nearly one-third of this cohort is without tumor recurrence at five years from diagnosis. A second clinical trial (NCT00639639) resulted in a 36% survival rate at five years from diagnosis. Results of the first two-arm trial (NCT00639639) showed increased migration of the DC vaccine to draining lymph nodes, and this increased migration has been recapitulated in our larger confirmatory clinical study (NCT02366728). We have now observed that nearly one-third of the GBM study patient population receiving CMV-specific DC vaccines results in exceptional long-term survivors.