Cancer immunotherapy by fusions of dendritic and tumour cells and rh-IL-12
Cancer immunotherapy by fusions of dendritic and tumour cells and rh-IL-12
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DOI：
10.1111/j.1365-2362.2005.01494.x
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发表时间：
2005-04-01
影响因子：
5.5
通讯作者：
Toda, G
中科院分区：
文献类型：
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作者：
Homma, S;Kikuchi, T;Toda, G
在小鼠实验模型中，用树突状细胞和肿瘤细胞组成的融合细胞（FCs）接种疫苗以及白介素-12 （IL-12）对已建立的肿瘤显示出显著的治疗效果。我们使用FCs和rhIL-12对多种恶性肿瘤进行了免疫治疗，并研究了治疗的安全性和有效性。材料和方法将患者的dc与自体辐照的肿瘤细胞混合，用50%聚乙二醇处理生成fc。皮下接种FCs， 2、6天后分别在相同部位注射30 ng kg（-1）的rhIL-12。该过程作为一个周期进行，其中三个周期每隔一周重复一次，组成一个疗程。疗程结束后，评估其安全性和治疗效果。结果最常见的不良反应是发热，第一周期26%的患者出现发热。白细胞减少28%，血清ALT升高25%。12例恶性脑肿瘤患者中有3例（25%）达到了部分缓解（PR），但其他恶性肿瘤患者的肿瘤没有消退。16例脑肿瘤患者中有13例（81%）表现为皮肤迟发性超敏反应。然而，除脑肿瘤外，16名恶性肿瘤患者中只有1名（6%）出现了这种反应。结论FC疫苗联合rhIL-12免疫治疗对部分脑肿瘤患者无严重不良反应，治疗效果良好。
Background Vaccination with fusion cells (FCs) comprising dendritic cells and tumour cells as well as administration of interleukin-12 (IL-12) showed a significant therapeutic effect against established tumours in mouse experimental models. We conducted immunotherapy against various malignant tumours using the FCs and rhIL-12, and investigated the safety and efficacy of the therapy.Materials and methods Patients' DCs were mixed with autologous irradiated tumour cells and treated with 50% polyethylene glycol to generate FCs. The FCs were inoculated intradermally, and then 30 ng kg(-1) of rhIL-12 was injected at the same sites 2 and 6 days later. This process was carried out as one cycle, and three of these cycles were repeated at 1-week intervals to comprise one course. After completing the course, its safety and therapeutic effects were estimated.Results The most frequently observed adverse event was fever, observed in 26% of patients in the first cycle. Decrease in white blood cell and an increase in serum ALT were observed in 28% and 25%, respectively. Three out of 12 patients with a malignant brain tumour (25%) achieved a partial response (PR), but other patients with a malignant tumour showed no regression of their tumours. Thirteen out of 16 patients with a brain tumour (81%) showed cutaneous delayed hypersensitivity responses. However, only one of 16 patients (6%) with a malignant tumour other than a brain tumour developed such responses.Conclusions Immunotherapy using a FC vaccine and rhIL-12 induced no serious adverse reactions, and provided good therapeutic responses in some of the patients with a brain tumour.