Schwarze Julia Katharina, Awada Gil, Cras Louise, Tijtgat Jens, Forsyth Ramses, Dufait Inès, Tuyaerts Sandra, Van Riet Ivan, Neyns Bart
Department of Medical Oncology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
Department of Anatomopathology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium.
Vaccines (Basel). 2020 Nov 10;8(4):670. doi: 10.3390/vaccines8040670.
Intratumoral (IT) myeloid dendritic cells (myDCs) play a pivotal role in re-licensing antitumor cytotoxic T lymphocytes. IT injection of the IgG monoclonal antibodies ipilimumab and avelumab may induce antibody-dependent cellular cytotoxicity, thereby enhancing the release of tumor antigens that can be captured and processed by CD1c (BDCA-1) myDCs. Patients with advanced solid tumors after standard care were eligible for IT injections of ≥1 lesion with ipilimumab (10 mg) and avelumab (40 mg) and intravenous (IV) nivolumab (10 mg) on day 1, followed by IT injection of autologous CD1c (BDCA-1) myDCs on day 2. IT/IV administration of ipilimumab, avelumab, and nivolumab was repeated bi-weekly. Primary objectives were safety and feasibility. Nine patients were treated with a median of 21 × 10 CD1c (BDCA-1) myDCs, and a median of 4 IT/IV administrations of ipilimumab, avelumab, and nivolumab. The treatment was safe with mainly injection-site reactions, but also immune-related pneumonitis ( = 2), colitis ( = 1), and bullous pemphigoid ( = 1). The best response was a durable partial response in a patient with stage IV melanoma who previously progressed on checkpoint inhibitors. Our combinatorial therapeutic approach, including IT injection of CD1c (BDCA-1) myDCs, is feasible and safe, and it resulted in encouraging signs of antitumor activity in patients with advanced solid tumors.
肿瘤内（IT）髓样树突状细胞（myDCs）在重新激活抗肿瘤细胞毒性T淋巴细胞中起关键作用。瘤内注射IgG单克隆抗体伊匹单抗和阿维鲁单抗可能诱导抗体依赖性细胞毒性，从而增强肿瘤抗原的释放，这些抗原可被CD1c（BDCA-1）myDCs捕获和处理。标准治疗后患有晚期实体瘤的患者有资格在第1天对≥1个病灶进行瘤内注射伊匹单抗（10 mg）和阿维鲁单抗（40 mg）以及静脉注射（IV）纳武单抗（10 mg），随后在第2天瘤内注射自体CD1c（BDCA-1）myDCs。伊匹单抗、阿维鲁单抗和纳武单抗的瘤内/静脉给药每两周重复一次。主要目标是安全性和可行性。9名患者接受了中位数为21×10个CD1c（BDCA-1）myDCs的治疗，以及中位数为4次伊匹单抗、阿维鲁单抗和纳武单抗的瘤内/静脉给药。该治疗是安全的，主要有注射部位反应，但也有免疫相关肺炎（ = 2）、结肠炎（ = 1）和大疱性类天疱疮（ = 1）。最佳反应是一名先前在检查点抑制剂治疗中进展的IV期黑色素瘤患者出现持久部分缓解。我们的联合治疗方法，包括瘤内注射CD1c（BDCA-1）myDCs，是可行且安全的，并且在晚期实体瘤患者中产生了令人鼓舞的抗肿瘤活性迹象。
