Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma
Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma
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DOI：
10.1097/01.cji.0000154248.74383.5e
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发表时间：
2005-03-01
影响因子：
3.9
通讯作者：
Hsieh, SL
中科院分区：
文献类型：
--
作者：
Chi, KW;Liu, SD;Hsieh, SL
本研究旨在评估自体未成熟树突状细胞（DC）直接注射入晚期肝癌患者放疗后的安全性和诱导的免疫应答。入组了不适合手术或经动脉栓塞的晚期/转移性肝癌患者。两组患者接受了两次疫苗接种。每次疫苗接种包括在8戈伊的单次适形放疗后2天瘤内注射自体未成熟DC，分为4个剂量组，5 × 10（6）、1.5 × 10（7）、3 × 10（7）和5 × 10（7）个细胞。3周后进行第二次接种。在进入的14名患者中，12名完成了两个周期的疫苗接种。在任何剂量水平下，治疗均耐受良好。DC注射后，6名患者出现轻度一过性发热（1-2级）伴寒战反应，3名患者出现I级疲劳，1名患者出现轻度肌痛和关节痛。没有临床表现的自身免疫性疾病的证据。有两个部分答复和四个次要答复。甲胎蛋白（AFP）水平下降超过50%，发现在三名患者。10例患者在第二个接种周期后2周完成了免疫应答评价。AFP特异性免疫应答在8例细胞因子释放试验和7例ELISPOT试验中明显。6例患者在接种疫苗后表现出NK细胞细胞毒活性增加。这些数据表明，腔内注射DC和适形放射治疗相结合是安全的，可以诱导肿瘤特异性和天然免疫。
A phase I study was conducted to assess the safety and immunologic response induced by direct injection of autologous immature dendritic cells (DCs) into tumor under radiotherapy in advanced hepatoma patients. Patients with advanced/rnetastatic stage hepatoma not suitable for surgery or transarterial embolization were enrolled. Groups of patients received two vaccinations. Each vaccination consisted of intratumoral injections of autologous immature DCs in four dose cohorts of 5 X 10(6), 1.5 X 10(7) 3 X 10(7), and 5 X 10(7) cells 2 days after a single fraction of conformal radiotherapy of 8 Gy. The second vaccination was performed 3 weeks later. Of the 14 patients entered, 12 completed two cycles of vaccination. The treatment was well tolerated at any of the dose levels. Six patients had mild transient fever (grade 1-2) with chill reactions, three patients developed grade I fatigue, and one patient developed mild myalgia and arthralgia after DC injections. There was no evidence of clinically manifested autoimmune disease. There were two partial responses and four minor responses. A decrease in the alpha-fetoprotein (AFP) level of more than 50% was found in three patients. Ten patients had completed immunologic response evaluation 2 weeks after the second cycle of vaccination. The AFP-specific immune response was evident in eight patients examined by cytokine release assay and in seven patients by ELISPOT assay. Six patients showed an increased NK cell cytotoxic activity after vaccination. These data suggest that the combination of intraturnoral injection of DCs and conformal radiotherapy is safe and can induce tumor-specific and innate immunity.