恶性胸膜间皮瘤（MPM）是一种侵袭性癌症，预后非常差。最近，免疫检查点抑制 (ICI) 已成为当前正在进行的革命的中心舞台，这场革命正在改变包括 MPM 在内的多种恶性肿瘤的护理标准治疗。由于多种论点和不断积累的证据支持化疗和免疫疗法之间以及不同类别的免疫疗法之间存在治疗协同作用，我们设计了一项多中心、单臂、I/II 期试验，其中-死亡配体 1 (PD-L1) 抑制和树突状细胞 (DC) 疫苗接种被整合到针对上皮样 MPM 患者的基于铂/培美曲塞的一线传统治疗方案中（Immuno-MESODEC，ClinicalTrials.gov 标识符 NCT05765084）。 15 名未接受过治疗的不可切除的上皮样亚型 MPM 患者将接受 4 个每 3 周（±3 天）的化疗免疫治疗周期。由顺铂 (75mg/m2) 和培美曲塞 (500mg/m2) 组成的标准护理化疗将辅以抗 PD-L1 抗体 atezolizumab (1200 mg) 和自体肾母细胞瘤 1 mRNA 电穿孔树突状细胞 (WT1) /DC) 疫苗接种（8-10 x 106 细胞/疫苗接种）。在化学免疫治疗方案完成后，可以任选地施用额外的atezolizumab (1680 mg)剂量和/或WT1/DC疫苗接种（8-10 x 106细胞/疫苗接种）。患者的随访将在最终 atezolizumab 给药和/或 WT1/DC 疫苗接种后持续长达 90 天，或在诊断后 24 个月（以较晚者为准）。该试验的主要终点是安全性和可行性，次要终点是临床疗效和免疫原性。该 I/II 期试验将评估在一线标准护理化疗中添加 atezolizumab 和 WT1/DC 疫苗接种来治疗上皮样 MPM 是否可行且安全。如果是这样，应该进一步研究这种新颖的组合策略，作为治疗这种难以治疗的癌症的一种有前途的先进治疗选择。版权所有：© 2024 Van den Bossche 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a very poor prognosis. Recently, immune checkpoint inhibition (ICI) has taken center stage in the currently ongoing revolution that is changing standard-of-care treatment for several malignancies, including MPM. As multiple arguments and accumulating lines of evidence are in support of the existence of a therapeutic synergism between chemotherapy and immunotherapy, as well as between different classes of immunotherapeutics, we designed a multicenter, single-arm, phase I/II trial in which both programmed-death-ligand 1 (PD-L1) inhibition and dendritic cell (DC) vaccination are integrated in the first-line conventional platinum/pemetrexed-based treatment scheme for epithelioid MPM patients (Immuno-MESODEC, ClinicalTrials.gov identifier NCT05765084). Fifteen treatment-naïve patients with unresectable epithelioid subtype MPM will be treated with four 3-weekly (±3 days) chemo-immunotherapy cycles. Standard-of-care chemotherapy consisting of cisplatinum (75mg/m2) and pemetrexed (500mg/m2) will be supplemented with the anti-PD-L1 antibody atezolizumab (1200 mg) and autologous Wilms' tumor 1 mRNA-electroporated dendritic cell (WT1/DC) vaccination (8-10 x 106 cells/vaccination). Additional atezolizumab (1680 mg) doses and/or WT1/DC vaccinations (8-10 x 106 cells/vaccination) can be administered optionally following completion of the chemo-immunotherapy scheme. Follow-up of patients will last for up to 90 days after final atezolizumab administration and/or WT1/DC vaccination or 24 months after diagnosis, whichever occurs later. The trial's primary endpoints are safety and feasibility, secondary endpoints are clinical efficacy and immunogenicity. This phase I/II trial will evaluate whether addition of atezolizumab and WT1/DC vaccination to frontline standard-of-care chemotherapy for the treatment of epithelioid MPM is feasible and safe. If so, this novel combination strategy should be further investigated as a promising advanced treatment option for this hard-to-treat cancer.Copyright: © 2024 Van den Bossche et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.