Bernhardt S L, Gjertsen M K, Trachsel S, Møller M, Eriksen J A, Meo M, Buanes T, Gaudernack G
Ullevål University Hospital, Oslo, Norway.
Br J Cancer. 2006 Dec 4;95(11):1474-82. doi: 10.1038/sj.bjc.6603437. Epub 2006 Oct 24.
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.
无法手术的胰腺癌患者预后不佳，平均预期寿命为3至6个月。因此迫切需要新的治疗方法。85%至90%的胰腺癌中可检测到端粒酶的表达，并且免疫原性端粒酶肽已得到鉴定。开展了一项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例不可切除胰腺癌患者接受了三种剂量水平的端粒酶肽GV1001皮内注射，并联合粒细胞巨噬细胞集落刺激因子。治疗期为10周。后续治疗提供每月一次的加强疫苗接种。通过迟发型超敏皮肤反应和体外T细胞增殖来测定免疫反应。GV1001耐受性良好。38例可评估患者中有24例观察到免疫反应，中等剂量组比例最高（75%）。27例可评估患者完成了研究。中等剂量组的中位生存期为8.6个月，显著长于低剂量组（P = 0.006）和高剂量组（P = 0.05）。中等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，值得进一步开展临床研究。
