Clinical trial of autologous formalin-fixed tumor vaccine for glioblastoma multiforme patients
Clinical trial of autologous formalin-fixed tumor vaccine for glioblastoma multiforme patients
复制标题
DOI：
10.1111/j.1349-7006.2007.00518.x
复制
发表时间：
2007-08-01
期刊：
影响因子：
5.7
通讯作者：
Ohno, Tadao
中科院分区：
文献类型：
--
作者：
Ishikawa, Eiichi;Tsuboi, Koji;Ohno, Tadao
进行了一项初步研究，以调查自体福尔马林固定肿瘤疫苗（AFTV）的安全性和可行性以及多形性胶质母细胞瘤（GBM）患者对这些疫苗的临床反应。招募了 12 名原发性 GBM 患者。八人患有复发性疾病，四人已接受原发性疾病治疗，但仍保留可见的肿瘤块。 AFTV由手术时获得的福尔马林固定和/或石蜡包埋的肿瘤组织制备，并与原始佐剂材料预混合。每周对患者进行 3 次五位点皮内接种。每次疫苗接种前后均进行迟发型超敏反应试验。此外，对肿瘤组织进行免疫组织化学分析，以确定 MIB-1、p53 和主要组织相容性复合物 (MHC) I 类复合物的表达是否可以预测对治疗的反应。治疗耐受性良好，仅报告局部红斑、硬结和低烧。在 12 名患者中，一名患者显示完全缓解，一名患者显示部分缓解，两名患者显示轻微缓解，一名患者病情稳定，七名患者病情进展。从 AFTV 治疗开始起，中位生存期为 10.7 个月，但 5 名应答者中有 3 人在 AFTV 接种后存活了 20 个月或更长时间。肿瘤的低 p53 和高 MHC I 类表达可能有助于预测该疗法的疗效。因此，AFTV是安全可行的，并且可以显着改善GBM的预后。非常需要进一步的临床研究来证实这一点。
A pilot study was performed to investigate the safety and feasibility of autologous formalin-fixed tumor vaccines (AFTV) and the clinical responses to these vaccines by glioblastoma multiforme (GBM) patients. Twelve primary GBM patients were recruited. Eight had recurrent disease while four had been treated for primary disease but retained a visible tumor mass. AFTV were prepared from formalin-fixed and/or paraffin-embedded tumor tissue obtained upon surgery and premixed with original adjuvant materials. The patients were given three five-site intradermal inoculations at weekly intervals. A delayed-type hypersensitivity test was performed before and after each vaccination. In addition, the tumor tissues were subjected to immunohistochemical analysis to determine whether MIB-1, p53, and major histocompatibility complex (MHC) class-I complex expression could predict the response to the treatment. The treatment was well tolerated, with only local erythema, induration, and low-grade fever being reported. Of the 12 patients, one showed a complete response, one showed a partial response, two showed minor responses, one had stable disease, and seven exhibited progressive disease. The median survival period was 10.7 months from the initiation of the AFTV treatment but three of the five responders survived for 20 months or more after AFTV inoculation. Low p53 and high MHC class-I expression by the tumor may help predict the efficacy of this therapy. Thus, the AFTV is safe and feasible, and could significantly improve the outcome of GBM. Further clinical investigations to confirm this are highly desirable.