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首页> 外文期刊>Journal of Translational Medicine >Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer
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Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

机译：基于Poxvirus的胰腺癌患者疫苗治疗

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Purpose An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival. Patients and methods Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM) (PANVAC-V) and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F). Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis. Results The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%). Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; P = .002). Conclusion Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer.
机译：目的，进行开放标签阶段1重组蛋白增强痘病毒的研究靶向CEA和MUC-1，以确定安全性，耐受性和获得免疫应答和存活的初步数据。患者和方法在I期临床试验中治疗了10例先进的胰腺癌患者。疫苗接种方案由表达肿瘤抗原癌丙烯抗原（CEA）和粘蛋白-1（MUC-1）的痘苗病毒组成，具有三个共刺激分子B7.1，ICAM-1和LFA-3（TRICOM）（PANVAC-V）和禽类病毒表达相同的抗原和共刺激分子（Panvac-F）。患者用Panvac-V涂有Panvac-V，然后使用Panvac-F的三种加强疫苗接种。粒细胞 - 巨噬细胞菌落刺激因子（GM-CSF）用作每次疫苗接种后的局部佐剂，然后连续3天。为没有渐进性疾病的患者提供每月增强疫苗接种最长12个月。在免疫分析的疫苗疫苗之前，期间和之后收集外周血。结果最常见的治疗相关不良事件是轻度注射部位反应。在所有10名患者中观察到针对痘苗病毒的抗体反应，并在8名可评估患者中的5例中观察到抗原特异性T细胞应答（62.5％）。中位数总生存率为6.3个月，与没有（分别为15.1 vs 3.9个月的人）产生抗CEA-和/或MUC-1特异性免疫应答的患者，对整体存活率显着增加。 ）。结论痘病毒疫苗接种是安全，耐受性，能够在晚期胰腺癌患者中产生抗原特异性免疫应答。

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