Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant:: Clinical and immunological responses in patients with pancreatic adenocarcinoma
Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant:: Clinical and immunological responses in patients with pancreatic adenocarcinoma
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DOI：
10.1002/ijc.1205
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发表时间：
2001-05-01
影响因子：
6.4
通讯作者：
Gaudernack, G
中科院分区：
文献类型：
--
作者：
Gjertsen, MK;Buanes, T;Gaudernack, G
K-ras基因突变常见于胰腺癌，因此诱导对突变ras基因的免疫对胰腺癌患者可能有临床益处。我们介绍了一项临床I/II期试验的数据，该试验涉及胰腺癌患者接受I.D.疫苗接种。人工合成突变型RAS多肽联合粒细胞-巨噬细胞集落刺激因子注射。48名患者(10名手术切除，38名晚期疾病)在门诊基础上接受治疗。在43名可评估的患者中，有25名(58%)被诱导了多肽特异性免疫，这表明所使用的方案非常有效，即使在终末期疾病的患者中也能够诱导免疫反应。对患者较长时间的跟踪显示，有证据表明，针对ras突变，患者可以诱导长期的免疫记忆。同样存在于肿瘤中的与Arg12突变反应的CD4(+)T细胞可以从肿瘤活检中分离出来，这表明激活的ras特异性T细胞能够选择性地在肿瘤中积聚。所有患者对疫苗的耐受性都很好，对多肽疫苗表现出免疫应答的晚期癌症患者从治疗开始就显示出比无效者更长的生存期(中位生存期分别为148d和61d；P=0.0002)，尽管我们的研究包括了有限数量的患者，但延长的生存期和对疫苗的免疫反应之间的关联表明，ras多肽疫苗接种可能对这类患者获得临床益处。(C)2001年Wiley-Liss，Inc.
K-RAS mutations are frequently found in adenocarcinomas of the pancreas, and induction of immunity against mutant ras can therefore be of possible clinical benefit in patients with pancreatic cancer. We present data from a clinical phase I/II trial involving patients with adenocarcinoma of the pancreas vaccinated by i.d. injection of synthetic mutant ras peptides in combination with granulocyte-macrophage colony-stimulating Factor. Forty-eight patients(10 surgically resected and 38 with advanced disease) were treated on an outpatient basis. Peptide-specific immunity was induced in 25 of 43 (58%) evaluable patients, indicating that the protocol used is very potent and capable of eliciting immune responses even in patients with end-stage disease. Patients followed-up for longer periods showed evidence of induction of long-lived immunological memory against the ras mutations. CD4(+) T cells reactive with an Arg12 mutation also present in the tumor could be isolated from a tumor biopsy, demonstrating that activated, ras-specific T cells were able to selectively accumulate in the tumor. Vaccination was well tolerated in all patients, Patients with advanced cancer demonstrating an immune response to the peptide vaccine showed prolonged survival from the start of treatment compared to non-responders (median survival 148 days vs, 61 days, respectively; P = 0.0002), Although a limited number of patients were included in our study, the association between prolonged survival and an immune response against the vaccine suggests that a clinical benefit of ras peptide vaccination may be obtained for this group of patients. (C) 2001 Wiley-Liss, Inc.