Yamanaka R, Abe T, Yajima N, Tsuchiya N, Homma J, Kobayashi T, Narita M, Takahashi M, Tanaka R
Department of Neurosurgery, Brain Research Institute, Niigata University, Asahimachi-dori 1-757, Niigata City, 951-8585, Japan.
Br J Cancer. 2003 Oct 6;89(7):1172-9. doi: 10.1038/sj.bjc.6601268.
In this Phase I/II trial, the patient's peripheral blood dendritic cells were pulsed with an autologous tumour lysate of the glioma. Seven patients with glioblastoma and three patients with anaplastic glioma, ranging in age from 20 to 69 years, participated in this study. The mean numbers of vaccinations of tumour lysate-pulsed dendritic cells were 3.7 times intradermally close to a cervical lymph node, and 3.2 times intratumorally via an Ommaya reservoir. The percentage of CD56-positive cells in the peripheral blood lymphocytes increased after immunisation. There were two minor responses and four no-change cases evaluated by radiological findings. Dendritic cell vaccination elicited T-cell-mediated antitumour activity, as evaluated by the ELISPOT assay after vaccination in two of five tested patients. Three patients showed delayed-type hypersensitivity reactivity to the autologous tumour lysate, two of these had a minor clinical response, and two had an increased ELISPOT result. Intratumoral CD4+ and CD8+ T-cell infiltration was detected in two patients who underwent reoperation after vaccination. This study demonstrated the safety and antitumour effects of autologous tumour lysate-pulsed dendritic cell therapy for patients with malignant glioma.
在这项I/II期试验中，用神经胶质瘤的自体肿瘤裂解物刺激患者的外周血树突状细胞。7例胶质母细胞瘤患者和3例间变性神经胶质瘤患者参与了本研究，年龄在20至69岁之间。肿瘤裂解物刺激的树突状细胞的平均接种次数为：皮内靠近颈部淋巴结3.7次，通过Ommaya储液器瘤内接种3.2次。免疫后外周血淋巴细胞中CD56阳性细胞的百分比增加。根据影像学检查结果评估，有2例轻微反应和4例无变化病例。通过对5例受试患者中的2例接种后进行ELISPOT分析评估，树突状细胞疫苗接种引发了T细胞介导的抗肿瘤活性。3例患者对自体肿瘤裂解物表现出迟发型超敏反应，其中2例有轻微临床反应，2例ELISPOT结果升高。在接种后接受再次手术的2例患者中检测到瘤内CD4 +和CD8 + T细胞浸润。本研究证明了自体肿瘤裂解物刺激的树突状细胞疗法对恶性神经胶质瘤患者的安全性和抗肿瘤作用。
