Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer
Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer
复制标题
DOI：
10.1215/s1152851703000668
复制
发表时间：
2004-07-01
期刊：
影响因子：
15.9
通讯作者：
Ashley, DA
中科院分区：
文献类型：
--
作者：
Caruso, DA;Orme, LM;Ashley, DA
我们对9例复发性脑肿瘤患儿进行了1期研究，使用肿瘤RNA脉冲的单核细胞来源的树突状细胞制备抗肿瘤疫苗（DCRNA）制剂。本研究的目的包括（1）确定安全性和可行性，以及（2）测量DCRNA后一般、抗原特异性和肿瘤特异性免疫应答的变化。树突状细胞来源于与IL-4和粒细胞-巨噬细胞集落刺激因子培养7天后新鲜分离的单核细胞，用自体肿瘤RNA脉冲，然后冷冻保存。患者接受至少3种疫苗，每种疫苗包括每两周一次的静脉内和皮内接种。该研究表明，这种从单一白细胞分离产品中生产和施用DCRNA的方法在该儿科脑肿瘤人群中既可行又安全。所有受试患者在入组研究时的免疫功能均受损。虽然所有患者对回忆抗原（白喉和破伤风）的体液反应都是完整的，但对有丝分裂原和回忆抗原的细胞反应低于正常。DCRNA疫苗接种后，7例患者中有2例表现出稳定的临床疾病，7例患者中有1例表现出部分应答。7名接受测试的患者中有2名显示出对DCRNA的肿瘤特异性免疫应答。这项研究表明，DCRNA疫苗在中枢神经系统肿瘤儿童中是安全可行的，只需进行一次白细胞分离。
We conducted a phase 1 study of 9 pediatric patients with recurrent brain tumors using monocyte-derived dendritic cells pulsed with tumor RNA to produce antitumor vaccine (DCRNA) preparations. The objectives of this study included (1) establishing safety and feasibility and (2) measuring changes in general, antigen-specific, and tumor-specific immune responses after DCRNA. Dendritic cells were derived from freshly isolated monocytes after 7 days of culture with IL-4 and granulocyte-macrophage colony-stimulating factor, pulsed with autologous tumor RNA, and then cryopreserved. Patients received at least 3 vaccines, each consisting of an intravenous and an intradermal administration at biweekly intervals. The study showed that this method for producing and administering DCRNA from a single leukapheresis product was both feasible and safe in this pediatric brain tumor population. Immune function at the time of enrollment into the study was impaired in all patients tested. While humoral responses to recall antigens (diphtheria and tetanus) were intact in all patients, cellular responses to mitogen and recall antigens were below normal. Following DCRNA vaccine, 2 of 7 patients showed stable clinical disease and I of 7 showed a partial response. Two of 7 patients who were tested showed a tumor-specific immune response to DCRNA This study showed that DCRNA vaccines are both safe and feasible in children with tumors of the central nervous system with a single leukapheresis.