Dendritic cells are essential for priming but inefficient for boosting antitumour immune response in an orthotopic murine glioma model
Dendritic cells are essential for priming but inefficient for boosting antitumour immune response in an orthotopic murine glioma model
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DOI：
10.1007/s00262-005-0040-7
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发表时间：
2006-03-01
影响因子：
5.8
通讯作者：
Puisieux, I
中科院分区：
文献类型：
--
作者：
Jouanneau, E;Poujol, D;Puisieux, I
恶性神经胶质瘤的预后仍然不佳，需要替代的治疗策略。使用肿瘤抗原脉冲的树突状细胞（DC）进行免疫治疗成为一种有前途的方法。许多参数会影响 DC 疫苗的功效，需要在临床前模型中进行优化。本研究比较了使用负载肿瘤细胞裂解物（DC-Lysate）的 DC 的不同疫苗方案，以提高 GL26 原位鼠神经胶质瘤模型的长期存活率，重点关注注射次数和回忆抗肿瘤免疫反应的最佳方式。与未接种疫苗的动物相比，双重接种 DC-Lysate 显着延长了中位生存期（平均生存期 87.5 天与 25 天；p < 0.0001）。体外数据显示针对 GL26 的特异性细胞毒活性。然而，晚期肿瘤经常在3个月后复发，只有20%的小鼠在7个月时最终治愈。虽然一次、两次或三次 DC 注射可产生相同的存活率，但与双次 DC-Lysate 组相比，在初次 DC-Lysate 启动后仅使用肿瘤裂解物进行加强，可显着改善接种疫苗的小鼠的长期存活率，67.5% 的动物在 7 个月时治愈（p < 0.0001）。体外数据显示 DC-Lysate/Lysate 组具有更好的特异性 CTL 反应以及特异性抗 GL26 抗体的诱导，从而介导补体依赖性细胞毒性。这些实验数据对于目前使用多次 DC 注射的临床试验的设计可能很重要。
The prognosis of malignant gliomas remains dismal and alternative therapeutic strategies are required. Immunotherapy with dendritic cells (DCs) pulsed with tumour antigens emerges as a promising approach. Many parameters influence the efficacy of DC-based vaccines and need to be optimised in preclinical models. The present study compares different vaccine schedules using DCs loaded with tumour cell lysate (DC-Lysate) for increasing long-term survival in the GL26 orthotopic murine glioma model, focusing on the number of injections and an optimal way to recall antitumour immune response. Double vaccination with DC-Lysate strongly prolonged median survival compared to unvaccinated animals (mean survival 87.5 daysvs. 25 days; p < 0.0001). In vitro data showed specific cytotoxic activity against GL26. However, late tumour relapses frequently Occurred after 3 months and only 20% of mice were finally cured at 7 months. While one, two or three DC injections gave identical survival, a boost using only tumour lysate after initial DC-Lysate priming dramatically improved long-term survival in vaccinated mice, compared to the double DC-Lysate group, with 67.5% of animals cured at 7 months (p < 0.0001). In vitro data showed better specific CTL response and also the induction of specific anti-GL26 antibodies in the DC-Lysate/Lysate group, which mediated Complement Dependent Cytotoxicity. These experimental data may be of importance for the design of clinical trials that currently use multiple DC injections.