He Zixuan, Wang Shuo, Qiao Guoliang, Wang Xiaoli, Zhou Xinna, Zhu Siyu, Yuan Yanhua, Morse Michael A, Hobeika Amy, Ren Jun, Lyerly Herbert Kim
Department of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University Beijing 100038, China.
Department of Medicine, Duke University Medical Center Durham, NC 27710, USA.
Am J Transl Res. 2020 Jul 15;12(7):3940-3952. eCollection 2020.
To explore the safety and efficacy of intra-cavitary infusions of autologous mixed dendritic cell (DC)-cytokine-induced killer (CIK) cell products in advanced cancer patients with malignant pleural effusions or ascites. DC-CIKs were expanded ex vivo (mean yield of 1.36×10 cells (range, 0.74~4.98×10)) from peripheral blood mononuclear cells obtained by repeated venipuncture or apheresis. Patients received at least 1 cycle of 3 infusions of the DC-CIKs administered by indwelling catheter into the pleural or peritoneal cavity every other day. The volume of malignant effusions was assessed radiologically. Peripheral blood lymphocyte populations were enumerated by flow cytometry. Quality of life (QoL) during the DC-CIK infusions was assessed by the EORTC QLQ-30 instrument. ctDNA sequencing was performed to analyze gene clonal load and molecular tumor burden during the infusion treatment. Thirty-seven patients with breast, lung and other malignancies were enrolled. The results showed that intra-cavitary DC-CIK infusions (16 intrapleural and 21 intraperitoneal) were well-tolerated with no grade 3/4 adverse events. There was one complete response with effusion disappearance (CR) (3%), 13 partial responses (PR) (35%), 12 with stable disease (SD) (32%) and 11 with progressive disease (PD) (30%), resulting in a clinical effusion control rate (CCR) of 70% (26/37). The total number of infused CIKs and the CD3+/CD8+ and CD8+/CD28+ T cell frequencies within the CIKs were associated with effusion control (P=0.013). Moreover, increased peripheral blood CD3+/CD8+ (P=0.035) and decreased CD4+/CD25+ T cell frequencies (P=0.041) following the DC-CIK infusions were associated with malignant effusion and ascites control. Reductions in ctDNA correlated with clinical benefit. In conclusion, intra-cavitary autologous cellular immunotherapy is an alternative method to effectively control malignant pleural effusions and ascites. The overall effusion control rate was associated with higher peripheral blood effector T cell frequencies.
探讨腔内输注自体混合树突状细胞（DC）-细胞因子诱导的杀伤细胞（CIK）产品对晚期恶性胸腔积液或腹水癌症患者的安全性和有效性。DC-CIK细胞由通过重复静脉穿刺或单采获得的外周血单个核细胞体外扩增（平均产量为1.36×10个细胞（范围为0.74~4.98×10））。患者接受至少1个周期，共3次输注DC-CIK细胞，通过留置导管隔日注入胸腔或腹腔。通过影像学评估恶性胸腔积液的量。通过流式细胞术对外周血淋巴细胞亚群进行计数。在DC-CIK细胞输注期间，采用欧洲癌症研究与治疗组织核心生活质量问卷（EORTC QLQ-30）评估生活质量（QoL）。在输注治疗期间进行循环肿瘤DNA（ctDNA）测序，以分析基因克隆负荷和分子肿瘤负担。纳入37例患有乳腺癌、肺癌和其他恶性肿瘤的患者。结果显示，腔内DC-CIK细胞输注（16例胸腔内输注和21例腹腔内输注）耐受性良好，无3/4级不良事件。有1例完全缓解（CR）（积液消失）（3%），13例部分缓解（PR）（35%），12例病情稳定（SD）（32%），11例病情进展（PD）（30%），临床积液控制率（CCR）为70%（26/37）。输注的CIK细胞总数以及CIK细胞内CD3+/CD8+和CD8+/CD28+ T细胞频率与积液控制相关（P=0.013）。此外，DC-CIK细胞输注后外周血CD3+/CD8+升高（P=0.035）和CD4+/CD25+ T细胞频率降低（P=0.041）与恶性胸腔积液和腹水控制相关。ctDNA的减少与临床获益相关。总之，腔内自体细胞免疫治疗是有效控制恶性胸腔积液和腹水的一种替代方法。总体积液控制率与外周血效应T细胞频率较高相关。
