A phase I pilot study of autologous heat shock protein vaccine HSPPC-96 in patients with resected pancreatic adenocarcinoma
A phase I pilot study of autologous heat shock protein vaccine HSPPC-96 in patients with resected pancreatic adenocarcinoma
复制标题
DOI：
10.1007/s10620-006-9205-2
复制
发表时间：
2007-08-01
影响因子：
3.1
通讯作者：
Brennan, Murray F.
中科院分区：
文献类型：
--
作者：
Maki, Robert G.;Livingston, Philip O.;Brennan, Murray F.
我们进行了I期初步研究以确定自体疫苗HSPPC-96（gp 96，Oncophage（R））是否可以从完全切除的胰腺腺癌中纯化，以确定患者对疫苗的耐受性并探索这些患者的免疫应答和临床结果。受试者每周用5 μ g自体HSPPC-96接种4剂。进行T细胞抗肿瘤反应性的系列ELISPOT测定。受试者既没有接受辅助化疗也没有接受放疗。10名患者接受了全程疫苗接种。未出现剂量限制性毒性。在液氮中立即冷冻肿瘤标本导致提高的疫苗产量。中位总生存期为2.2年（Kaplan-Meier估计）。自体抗HSPPC-96 ELISPOT反应性在检查的5例患者中的1例中显著增加，第二例的增加意义不明。在2.6、2.7和5.0年随访时，10例接受治疗的患者中有3例存活，无疾病。免疫应答与预后无明显相关性。本研究证明了从胰腺癌中制备HSPPC-96的可行性。使用多剂量水平检查这种新方法是进一步研究HSPPC-96疫苗接种在这种情况下的免疫原性和临床效用的一种方法。
We performed a phase I pilot study to determine if autologous vaccine HSPPC-96 (gp96, Oncophage (R)) could be purified from completely resected pancreas adenocarcinomas, to determine patient tolerance of vaccine and to explore immune responses and clinical outcomes of these patients. Subjects were vaccinated with 5 mu g of autologous HSPPC-96 weekly for 4 doses. Serial ELISPOT assays of T cells for antitumor reactivity were performed. Subjects received neither adjuvant chemotherapy nor radiation. Ten patients received a full course of vaccinations. No dose-limiting toxicities were encountered. Immediate freezing in liquid nitrogen of the tumor specimen resulted in improved vaccine yield. Median overall survival is 2.2 years (Kaplan-Meier estimate). Autologous anti-HSPPC-96 ELISPOT reactivity increased significantly in 1 of 5 patients examined and a second had an increase of unclear significance. Three of 10 treated patients are alive without disease at 2.6, 2.7, and 5.0 years follow-up. There was no observed correlation between immune response and prognosis. This study demonstrates the feasibility of preparing HSPPC-96 from pancreatic adenocarcinomas. Examination of this novel approach using multiple dose levels is 1 approach to further investigate the immunogenicity and clinical utility of HSPPC-96 vaccination in this setting.