Department of Medical BioSciences, Radboudumc, Nijmegen, Netherlands.
Department of Medical Oncology, Radboudumc, Nijmegen, Netherlands.
Front Immunol. 2024 Feb 20;15:1368103. doi: 10.3389/fimmu.2024.1368103. eCollection 2024.
Metastatic endometrial cancer (mEC) continues to have a poor prognosis despite the introduction of several novel therapies including immune checkpoints inhibitors. Dendritic cell (DC) vaccination is known to be a safe immunotherapeutic modality that can induce immunological and clinical responses in patients with solid tumors. Platinum-based chemotherapy is known to act synergistically with immunotherapy by selectively depleting suppressive immune cells. Therefore, we investigated the immunological efficacy of combined chemoimmunotherapy with an autologous DC vaccine and carboplatin/paclitaxel chemotherapy.
This is a prospective, exploratory, single-arm phase I/II study (NCT04212377) in 7 patients with mEC. The DC vaccine consisted of blood-derived conventional and plasmacytoid dendritic cells, loaded with known mEC antigens Mucin-1 and Survivin. Chemotherapy consisted of carboplatin/paclitaxel, given weekly for 6 cycles and three-weekly for 3 cycles. The primary endpoint was immunological vaccine efficacy; secondary endpoints were safety and feasibility.
Production of DC vaccines was successful in five out of seven patients. These five patients started study treatment and all were able to complete the entire treatment schedule. Antigen-specific responses could be demonstrated in two of the five patients who were treated. All patients had at least one adverse event grade 3 or higher. Treatment-related adverse events grade ≥3 were related to chemotherapy rather than DC vaccination; neutropenia was most common. Suppressive myeloid cells were selectively depleted in peripheral blood after chemotherapy.
DC vaccination can be safely combined with carboplatin/paclitaxel in patients with metastatic endometrial cancer and induces antigen-specific responses in a minority of patients. Longitudinal immunological phenotyping is suggestive of a synergistic effect of the combination.
尽管引入了几种新型疗法，包括免疫检查点抑制剂，转移性子宫内膜癌（mEC）的预后仍然很差。树突状细胞（DC）疫苗被认为是一种安全的免疫治疗方式，可在实体瘤患者中诱导免疫和临床反应。顺铂为基础的化疗通过选择性耗竭抑制性免疫细胞与免疫治疗具有协同作用。因此，我们研究了自体 DC 疫苗联合顺铂/紫杉醇化疗的联合化疗免疫治疗的免疫疗效。
这是一项针对 7 例 mEC 患者的前瞻性、探索性、单臂 I/II 期研究（NCT04212377）。DC 疫苗由血液来源的常规和浆细胞样树突状细胞组成，负载已知的 mEC 抗原 Mucin-1 和 Survivin。化疗包括每周给予 6 个周期和每 3 周给予 3 个周期的顺铂/紫杉醇。主要终点是免疫疫苗疗效；次要终点是安全性和可行性。
7 例患者中有 5 例成功生产出 DC 疫苗。这 5 例患者开始了研究治疗，并且都能够完成整个治疗计划。在接受治疗的 5 例患者中有 2 例可检测到抗原特异性反应。所有患者均至少发生 1 次 3 级或以上的不良事件。与治疗相关的 3 级或以上不良事件与化疗而非 DC 疫苗接种有关；最常见的是中性粒细胞减少症。化疗后外周血中抑制性髓样细胞被选择性耗竭。
DC 疫苗可与转移性子宫内膜癌患者的顺铂/紫杉醇安全联合使用，并在少数患者中诱导抗原特异性反应。纵向免疫表型分析提示联合具有协同作用。
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