Karcher Jochen, Dyckhoff Gerhard, Beckhove Philipp, Reisser Christoph, Brysch Michael, Ziouta Yvonne, Helmke Burkhard H, Weidauer Hagen, Schirrmacher Volker, Herold-Mende Christel
Department of Head and Neck Surgery, University of Heidelberg, Heidelberg, Germany.
Cancer Res. 2004 Nov 1;64(21):8057-61. doi: 10.1158/0008-5472.CAN-04-1545.
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.
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患者中是否可行且安全。此外,我们确定了其对无病生存期和总生存期的影响以及疫苗接种诱导的抗肿瘤反应性。在一项非随机的试点研究中,20例患者在术后进行了疫苗接种。疫苗是通过用新城疫病毒感染患者的肿瘤细胞培养物,然后进行γ射线照射而制备的,疫苗最多应用5次。通过迟发型超敏皮肤反应在皮肤中以及通过酶联免疫斑点测定法在血液中测定抗肿瘤免疫反应性。约80%的病例成功建立了肿瘤细胞培养物。疫苗接种后,我们未观察到严重的副作用。III期和IV期肿瘤接种疫苗患者(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,尤其是在无病患者中,并且在相当比例的接种疫苗患者中,即使在最后一次接种疫苗后5至7年,外周血中仍存在肿瘤反应性T细胞。用病毒修饰的自体肿瘤细胞进行术后疫苗接种似乎是可行且安全的,并且可能改善晚期肿瘤HNSCC患者的预后。我们观察到的抗肿瘤免疫反应,尤其是在长期存活患者中的反应,可能支持了这一点。