Antitumor vaccination in patients with head and neck squamous cell carcinomas with autologous virus-modified tumor cells
Antitumor vaccination in patients with head and neck squamous cell carcinomas with autologous virus-modified tumor cells
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DOI：
10.1158/0008-5472.can-04-1545
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发表时间：
2004-11-01
期刊：
影响因子：
11.2
通讯作者：
Herold-Mende, C
中科院分区：
文献类型：
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作者：
Karcher, J;Dyckhoff, G;Herold-Mende, C
晚期头颈部鳞状细胞癌（HNSCC）患者的预后仍然很差。因此，我们分析了用病毒修饰的自体肿瘤细胞疫苗进行抗肿瘤疫苗接种在HNSCC患者中是否可行和安全。此外，我们确定了对无病生存期和总生存期的影响以及疫苗诱导的抗肿瘤反应性。在一项非随机初步研究中，20例患者术后接种疫苗。通过用纽卡斯尔病病毒感染患者的肿瘤细胞培养物，然后进行γ射线照射来制备疫苗，并且疫苗施用多达五次。通过迟发型超敏反应皮肤反应和酶联免疫斑点试验测定皮肤中的抗肿瘤免疫反应性。在约80%的病例中，肿瘤细胞培养物的建立是成功的。接种疫苗后，我们没有观察到严重的副作用。接种疫苗的III期和IV期肿瘤患者（n = 18）的5年生存率为61%。免疫监测显示抗肿瘤迟发型超敏反应性显著增加，尤其是在无疾病患者中，并且在相当比例的接种疫苗的患者中，甚至在末次接种疫苗后5至7年，外周血中仍存在肿瘤反应性T细胞。术后接种病毒修饰的自体肿瘤细胞似乎是可行和安全的，并可能改善晚期肿瘤HNSCC患者的预后。我们观察到的抗肿瘤免疫应答支持了这一点，特别是在长期存活的患者中。
Prognosis of patients with advanced head and neck squamous cell carcinomas (HNSCC) is still poor. Therefore, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe in HNSCC patients. Furthermore, we determined the influence on disease-free survival and overall survival and the vaccination-induced antitumor reactivity. In a nonrandomized pilot study, 20 patients were vaccinated postoperatively. Vaccine was prepared from the tumor cell cultures of patients by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and vaccine was applied up to five times. Antitumor immune reactivity was determined in the skin by delayed type hypersensitivity skin reaction and in the blood by enzyme-linked immunospot assay. Establishment of tumor cell cultures was successful in about 80% of the cases. After vaccination, we observed no severe side effects. Percentages of survival of vaccinated patients with stage III and stage IV tumors (n = 18) were 61% at 5 years. Immune monitoring revealed significant increases of antitumor delayed type hypersensitivity reactivity especially in disease-free patients, and in a significant proportion of vaccinated patients the presence of tumor-reactive T-cells in the peripheral blood even 5 to 7 years after the last vaccination. Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and may improve the prognosis of HNSCC patients with advanced tumors. This could be supported by antitumor immune responses that we observed especially in long-term surviving patients.