Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras
Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras
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DOI：
10.1002/ijc.25449
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发表时间：
2011-03-01
影响因子：
6.4
通讯作者：
Buanes, Trond
中科院分区：
文献类型：
--
作者：
Weden, Synne;Klemp, Marianne;Buanes, Trond
K-ras突变经常在胰腺腺癌中发现，并可引起突变特异性免疫反应。靶向免疫系统对抗突变的Ras可能因此影响疾病的临床进程。在之前的两项I/II期临床试验中，23例胰腺癌手术切除后接种疫苗的患者（22例胰十二指肠切除术，1例远端切除术），就长期免疫t细胞反应性和生存率进行了超过10年的随访。该疫苗由合成的长突变ras肽组成，主要用于引发t辅助反应。20例可评估患者中有17例（85%）对疫苗有免疫应答。所有患者的中位生存期为27.5个月，免疫应答者为28个月。5年生存率分别为22%和29%。引人注目的是，10年生存率为20%（20例可评估患者中有4例），而同期接受治疗的未接种疫苗患者的10年生存率为零（0/87）。三名患者在接种疫苗后长达9年的时间里出现了记忆反应。目前对手术切除后的长期免疫反应和10年生存率的观察表明，K-ras疫苗接种可以巩固手术的效果，并代表未来的辅助治疗选择。
K-ras mutations are frequently found in adenocarcinomas of the pancreas and can elicit mutation-specific immune responses. Targeting the immune system against mutant Ras may thus influence the clinical course of the disease. Twenty-three patients who were vaccinated after surgical resection for pancreatic adenocarcinoma (22 pancreaticoduodenectomies, one distal resection), in two previous Phase I/II clinical trials, were followed for more than 10 years with respect to long-term immunological T-cell reactivity and survival. The vaccine was composed of long synthetic mutant ras peptides designed mainly to elicit T-helper responses. Seventeen of 20 evaluable patients (85%) responded immunologically to the vaccine. Median survival for all patients was 27.5 months and 28 months for immune responders. The 5-year survival was 22% and 29%, respectively. Strikingly, 10-year survival was 20% (four patients out of 20 evaluable) versus zero (0/87) in a cohort of nonvaccinated patient treated in the same period. Three patients mounted a memory response up to 9 years after vaccination. The present observation of long-term immune response together with 10-year survival following surgical resection indicates that K-ras vaccination may consolidate the effect of surgery and represent an adjuvant treatment option for the future.