Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study.
Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study.
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DOI：
10.1038/sj.bjc.6603437
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发表时间：
2006-12-04
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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作者：
患有无法手术的胰腺癌的患者预后不佳，平均预期寿命为3 - 6个月。因此迫切需要新的治疗方式。端粒酶在85 - 90%的胰腺癌中表达，并且免疫原性端粒酶肽已被鉴定。进行了一项I/II期研究以调查端粒酶肽疫苗接种的安全性、耐受性和免疫原性。同时记录患者的生存期。48名患有不可切除胰腺癌的患者接受了三种剂量水平的端粒酶肽GV1001皮内注射，并联合使用粒细胞 - 巨噬细胞集落刺激因子。治疗周期为10周。每月提供加强疫苗接种作为后续治疗。免疫反应通过迟发型超敏皮肤反应和体外T细胞增殖来测量。GV1001耐受性良好。在38名可评估患者中的24名观察到免疫反应，其中中剂量组的比例最高（75%）。27名可评估患者完成了研究。中剂量组的中位生存期为8.6个月，明显长于低剂量组（P = 0.006）和高剂量组（P = 0.05）。中剂量组可评估患者的1年生存率为25%。结果表明GV1001具有免疫原性且使用安全。生存期数据表明免疫反应的诱导与生存期延长相关，该疫苗可能为胰腺癌患者提供一种新的治疗选择，这鼓励了进一步的临床研究。
Patients with inoperable pancreatic cancer have a dismal prognosis with a mean life expectancy of 3–6 months. New treatment modalities are thus urgently needed. Telomerase is expressed in 85–90% of pancreas cancer, and immunogenic telomerase peptides have been characterised. A phase I/II study was conducted to investigate the safety, tolerability, and immunogenecity of telomerase peptide vaccination. Survival of the patients was also recorded. Forty-eight patients with non-resectable pancreatic cancer received intradermal injections of the telomerase peptide GV1001 at three dose levels, in combination with granulocyte–macrophage colony-stimulating factor. The treatment period was 10 weeks. Monthly booster vaccinations were offered as follow-up treatment. Immune responses were measured as delayed-type hypersensitivity skin reaction and in vitro T-cell proliferation. GV1001 was well tolerated. Immune responses were observed in 24 of 38 evaluable patients, with the highest ratio (75%) in the intermediate dose group. Twenty-seven evaluable patients completed the study. Median survival for the intermediate dose-group was 8.6 months, significantly longer for the low- (P=0.006) and high-dose groups (P=0.05). One-year survival for the evaluable patients in the intermediate dose group was 25%. The results demonstrate that GV1001 is immunogenic and safe to use. The survival data indicate that induction of an immune response is correlated with prolonged survival, and the vaccine may offer a new treatment option for pancreatic cancer patients, encouraging further clinical studies.
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DOI：
10.1084/jem.188.12.2357
发表时间：
1998-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hung K;Hayashi R;Lafond-Walker A;Lowenstein C;Pardoll D;Levitsky H
通讯作者：
Levitsky H
影响因子：
4.4
作者：
Markiewicz, MA;Fallarino, F;Gajewski, TF
通讯作者：
Gajewski, TF
影响因子：
4.4
作者：
Schurmans, LRHM;Diehl, L;Toes, REM
通讯作者：
Toes, REM
DOI：
10.1073/pnas.182418399
发表时间：
2002-09-17
影响因子：
11.1
作者：
Hernández, J;García-Pons, F;Zanetti, M
通讯作者：
Zanetti, M
影响因子：
6.4
作者：
Gjertsen, MK;Buanes, T;Gaudernack, G
通讯作者：
Gaudernack, G