Yamanaka Ryuya, Homma Junpei, Yajima Naoki, Tsuchiya Naoto, Sano Masakazu, Kobayashi Tsutomu, Yoshida Seiichi, Abe Takashi, Narita Miwako, Takahashi Masuhiro, Tanaka Ryuichi
Department of Neurosurgery, Brain Research Institute, Niigata University School of Medicine, Niigata University, Niigata, Japan.
Clin Cancer Res. 2005 Jun 1;11(11):4160-7. doi: 10.1158/1078-0432.CCR-05-0120.
To investigate the safety and the immunologic and clinical responses of dendritic cell therapy for patients with recurrent malignant glioma.
Twenty-four patients with recurrent malignant glioma (6 grade 3 and 18 grade 4 patients) were evaluated in a phase I/II clinical study of dendritic cell therapy. All patients were resistant to the standard maximum therapy. The patient's peripheral blood dendritic cells were generated with granulocyte macrophage colony-stimulating factor, plus interleukin 4 with or without OK-432, and pulsed with an autologous tumor lysate. Dendritic cells were injected intradermally, or both intratumorally and intradermally every 3 weeks.
The protocols were well tolerated with only local redness and swelling at the injection site in several cases. Clinical responses were as follows: 1 patient with partial response, 3 patients with minor response, 10 patients with stable disease, and 10 patients with progressive disease. The patients whose dendritic cells were matured with OK-432 had longer survival times than the dendritic cells from patients without OK-432 maturation. The patients with both intratumoral and intradermal administrations had a longer survival time than the patients with intradermal administration only. Increased ELISPOT and delayed-type hypersensitivity responses after vaccination could provide good laboratory markers to predict the clinical outcome of patients receiving dendritic cell vaccination. The overall survival of patients with grade 4 glioma was 480 days, which was significantly better than that in the control group.
This study showed the safety and clinical response of autologous tumor lysate-pulsed dendritic cell therapy for patients with malignant glioma. Dendritic cell therapy is recommended for further clinical studies in malignant glioma patients.
研究树突状细胞疗法对复发性恶性胶质瘤患者的安全性、免疫反应及临床反应。
在一项树突状细胞疗法的I/II期临床研究中，对24例复发性恶性胶质瘤患者（6例3级和18例4级患者）进行了评估。所有患者均对标准最大剂量治疗耐药。通过粒细胞巨噬细胞集落刺激因子加白细胞介素4（有或无OK-432）培养患者的外周血树突状细胞，并用自体肿瘤裂解物进行脉冲处理。每3周将树突状细胞皮内注射，或瘤内及皮内同时注射。
方案耐受性良好，仅几例患者在注射部位出现局部发红和肿胀。临床反应如下：1例部分缓解，3例轻度缓解，10例病情稳定，10例病情进展。用OK-432使树突状细胞成熟的患者比未用OK-432成熟的患者生存期更长。瘤内及皮内联合给药的患者比仅皮内给药的患者生存期更长。接种疫苗后ELISPOT增加和迟发型超敏反应增强可为预测接受树突状细胞疫苗接种患者的临床结局提供良好的实验室指标。4级胶质瘤患者的总生存期为480天，显著优于对照组。
本研究显示了自体肿瘤裂解物脉冲树突状细胞疗法对恶性胶质瘤患者的安全性和临床反应。推荐对恶性胶质瘤患者进行树突状细胞疗法的进一步临床研究。
