树突状细胞为基础的疫苗接种治疗晚期胰腺癌患者：一项初步研究结果。
Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: results of a pilot study.
机构信息
Medizinische Klinik Innenstadt, University of Munich, München, Germany.
出版信息
Cancer Immunol Immunother. 2011 Aug;60(8):1097-107. doi: 10.1007/s00262-011-1023-5. Epub 2011 May 6.
BACKGROUND AND AIMS
Dendritic cell (DC)-based vaccination can induce antitumor T cell responses in vivo. This clinical pilot study examined feasibility and outcome of DC-based tumor vaccination for patients with advanced pancreatic adenocarcinoma.
METHODS
Tumor lysate of patients with pancreatic carcinoma was generated by repeated freeze-thaw cycles of surgically obtained tissue specimens. Patients were eligible for DC vaccination after recurrence of pancreatic carcinoma or in a primarily palliative situation. DC were generated from peripheral blood mononuclear cells (PBMC), loaded with autologous tumor lysate, stimulated with TNF-α and PGE(2) and injected intradermally. All patients received concomitant chemotherapy with gemcitabine. Disease response was the primary endpoint. Individual immunological responses to DC vaccination were analyzed by T cell-based immunoassays using pre- and post-vaccination samples of non-adherent PBMC.
RESULTS
Twelve patients received DC vaccination and concomitant chemotherapy. One patient developed a partial remission, and two patients remained in stable disease. Median survival was 10.5 months. No severe side effects were observed. Tumor-reactive T cells could be detected prior to vaccination. DC vaccination increased the frequency of tumor-reactive cells in all patients tested; however, the degree of this increase varied. To quantify the presence of tumor-reactive T cells, stimulatory indices (SI) were calculated as the ratio of proliferation-inducing capacity of lysate-loaded versus -unloaded DC. The patient with longest overall survival of 56 months had a high SI of 6.49, indicating that the presence of a pre-vaccination antitumor T cell response might be associated with prolonged survival. Five patients survived 1 year or more.
CONCLUSION
DC-based vaccination can stimulate an antitumoral T cell response in patients with advanced or recurrent pancreatic carcinoma receiving concomitant gemcitabine treatment.
背景与目的
树突状细胞（DC）疫苗接种可在体内诱导抗肿瘤 T 细胞反应。本临床初步研究探讨了晚期胰腺腺癌患者使用基于树突状细胞的肿瘤疫苗接种的可行性和结果。
方法
通过对手术获得的组织标本进行反复冻融循环生成胰腺癌细胞裂解物。在胰腺腺癌复发或姑息治疗的情况下，患者有资格接受 DC 疫苗接种。从外周血单核细胞（PBMC）中生成 DC，用自体肿瘤裂解物负载，用 TNF-α和 PGE（2）刺激，皮内注射。所有患者均接受吉西他滨联合化疗。疾病反应是主要终点。通过使用接种前和接种后的非粘附性 PBMC 样本进行基于 T 细胞的免疫测定分析个体对 DC 疫苗接种的免疫反应。
结果
12 例患者接受了 DC 疫苗接种和联合化疗。1 例患者出现部分缓解，2 例患者病情稳定。中位生存期为 10.5 个月。未观察到严重副作用。在接种前可检测到肿瘤反应性 T 细胞。在所有接受测试的患者中，DC 疫苗接种均增加了肿瘤反应性细胞的频率；然而，这种增加的程度有所不同。为了定量存在肿瘤反应性 T 细胞，计算了刺激指数（SI）作为负载和未负载裂解物的 DC 的增殖诱导能力的比值。总体生存时间最长的 56 个月的患者 SI 为 6.49，表明接种前存在抗肿瘤 T 细胞反应可能与延长生存时间有关。有 5 例患者存活 1 年以上。
结论
在接受吉西他滨治疗的晚期或复发性胰腺腺癌患者中，基于树突状细胞的疫苗接种可刺激抗肿瘤 T 细胞反应。
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