Dumoulin Daphne W, Cornelissen Robin, Bezemer Koen, Baart Sara J, Aerts Joachim G J V
Department of Pulmonary Medicine, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
Department of Biostatistics, Erasmus MC, 3015 GD Rotterdam, The Netherlands.
Vaccines (Basel). 2021 May 19;9(5):525. doi: 10.3390/vaccines9050525.
Malignant pleural mesothelioma (MPM) is a fatal neoplasm with, if untreated, poor survival of approximately nine months from diagnosis. Until recently, phase II-III immunotherapy trials did not show any significant benefit. The lack of immunotherapy efficacy can be explained by the fact that mesothelioma is a tumor with an "immune desert" phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. By administration of DCs, which were ex-vivo cultured, exposed to (tumor-associated) antigens, and subsequently activated, this "immune desert" phenotype might be turned into an "inflamed" phenotype. Three phase I/II studies have been performed and published using activated DCs, which support this concept. We here report on the long-term survival of patients treated with DCs in three phase I/II studies.
Survival data of the phase I/II trials using DC therapy in MPM patients were obtained and subsequently analyzed. In the first two trials, DCs were loaded with autologous tumor lysate. In the third trial, DCs were loaded with allogeneic mesothelioma tumor cell line lysate.
In the three studies combined, 29 patients with MPM were treated with DC vaccination between 2006 and 2015. At data cut-off, the median OS was 27 months (95% CI: 21-47 months). OS at 2 years was 55.2% (95% CI: 39.7-76.6%), and OS at 5 years was 20.7% (95% CI: 10.1-42.2%).
The long-term survival of DC therapy in MPM in these three trials is promising, which is the basis for the randomized phase II/III DENIM study. This DENIM study is currently enrolling, and the results of which have to be awaited for definite conclusions.
恶性胸膜间皮瘤（MPM）是一种致命的肿瘤，如果不进行治疗，从诊断起生存期约为9个月，预后较差。直到最近，II-III期免疫治疗试验均未显示出任何显著益处。免疫治疗缺乏疗效可归因于间皮瘤是一种具有“免疫沙漠”表型的肿瘤，即一种以低T细胞浸润为特征的非炎症性肿瘤。通过给予体外培养、暴露于（肿瘤相关）抗原并随后激活的树突状细胞（DC），这种“免疫沙漠”表型可能会转变为“炎症”表型。已经进行并发表了三项使用活化DC的I/II期研究，这些研究支持了这一概念。我们在此报告三项I/II期研究中接受DC治疗的患者的长期生存情况。
获取并随后分析MPM患者使用DC疗法的I/II期试验的生存数据。在前两项试验中，DC负载自体肿瘤裂解物。在第三项试验中，DC负载异体间皮瘤肿瘤细胞系裂解物。
在这三项研究中，2006年至2015年间共有29例MPM患者接受了DC疫苗接种。在数据截止时，中位总生存期（OS）为27个月（95%置信区间：21-47个月）。2年时的OS为55.2%（95%置信区间：39.7-76.6%），5年时的OS为20.7%（95%置信区间：10.1-42.2%）。
这三项试验中DC疗法在MPM中的长期生存情况很有前景，这是随机II/III期DENIM研究的基础。这项DENIM研究目前正在招募患者，其结果有待观察才能得出明确结论。
