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首页> 外文期刊>American Journal of Translational Research >Clinical efficacy of intra-cavitary infusions of autologous dendritic cell/cytokine-induced killer cell products for the treatment of refractory malignant pleural effusions and ascites
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Clinical efficacy of intra-cavitary infusions of autologous dendritic cell/cytokine-induced killer cell products for the treatment of refractory malignant pleural effusions and ascites

机译：自体树突状细胞/细胞因子诱导杀伤细胞产物的腔内输注的临床疗效，用于治疗难治性恶性胸腔积液和腹水

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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 9 cells (range, 0.74~4.98×10 9 )) 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.
机译：探讨在晚期癌症患者中的自体混合树突状细胞（DC） - 胞嘧啶诱导的杀伤剂（CIK）细胞产物在恶性胸腔积液或腹水中的安全性混合细胞（DC） - 胞嘧啶诱导的杀伤剂（CIK）细胞产物的安全性和有效性。从反复静脉穿刺或采血间获得的外周血单核细胞，DC-CIKS扩展前体内（平均产量为1.36×10 9个细胞（范围，0.74〜4.98×10 9））。患者在每隔一天接受留置导管给予胸膜或腹腔腔内的DC-CIKS的3个循环的3个循环。显着评估恶性生效的体积。通过流式细胞术来列举外周血淋巴细胞群。通过EORTC QLQ-30仪器评估DC-CIK输注期间的寿命质量（QOL）。进行CTDNA测序以分析输注处理期间基因克隆载荷和分子肿瘤负荷。患有37名乳腺癌，肺等恶性肿瘤患者。结果表明，空腔内的DC-CIK输注（16个闭嘴腹膜内腹膜内）耐受良好耐受，没有3/4级不良事件。具有稳定性疾病（SD）（32％）和11例患病性（PD）（Pd）（Pd）（30％）（30％）（30％）（30％）（30％）（30％）（30％） ，导致临床活力控制率（CCR）为70％（26/37）。 CIKS内的注入CIK的总数和CD3 + / CD8 +和CD8 + / CD28 + T细胞频率与积液控制相关（P = 0.013）。此外，在DC-CIK输注后，增加外周血CD3 + / CD8 +（P = 0.035）和降低的CD4 + / CD25 + T细胞频率（P = 0.041）与恶性积液和腹水控制相关。减少CTDNA与临床效益相关。总之，腔内自体细胞免疫疗法是有效控制恶性胸腔积液和腹水的替代方法。整体积液控制率与较高的外周血效应器T细胞频率有关。

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