Wilms tumor gene (WT1) peptide-based cancer vaccine combined with gemcitabine for patients with advanced pancreatic cancer.
Wilms tumor gene (WT1) peptide-based cancer vaccine combined with gemcitabine for patients with advanced pancreatic cancer.
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DOI：
10.1097/cji.0000000000000020
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发表时间：
2014-02
期刊：
影响因子：
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通讯作者：
Sugiyama H
中科院分区：
文献类型：
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作者：
Nishida S;Koido S;Takeda Y;Homma S;Komita H;Takahara A;Morita S;Ito T;Morimoto S;Hara K;Tsuboi A;Oka Y;Yanagisawa S;Toyama Y;Ikegami M;Kitagawa T;Eguchi H;Wada H;Nagano H;Nakata J;Nakae Y;Hosen N;Oji Y;Tanaka T;Kawase I;Kumanogoh A;Sakamoto J;Doki Y;Mori M;Ohkusa T;Tajiri H;Sugiyama H
补充数字内容可在文本中找到。Wilms肿瘤基因（WT 1）蛋白是肿瘤免疫治疗的一个有吸引力的靶点。本研究旨在探讨吉西他滨联合WT 1肽疫苗治疗晚期胰腺癌的可行性，并对其临床疗效和免疫应答进行初步评价。入组了32例HLA-A*24：02+晚期胰腺癌患者。患者每两周皮内接受HLA-A*24：02限制性、修饰的9聚体WT 1肽（3 mg/体）与Montanide ISA 51佐剂（WT 1疫苗）乳化，并在28天周期的第1、8和15天接受吉西他滨（1000 mg/m2）。这种联合治疗耐受性良好。这种联合治疗的3-4级不良事件的频率与吉西他滨单药治疗的频率相似。客观缓解率为20.0%（6/30例可评价患者）。中位生存时间为8.1个月，1年生存率为29%。较长的生存期和WT 1肽的阳性迟发型超敏反应之间的相关性具有统计学意义，较长的生存期在治疗前后具有较高的记忆表型WT 1特异性细胞毒性T淋巴细胞的频率。WT 1疫苗联合吉西他滨治疗晚期胰腺癌患者耐受性良好。对WT 1肽的迟发型超敏反应阳性和记忆表型WT 1特异性细胞毒性T淋巴细胞的较高频率可能是吉西他滨和WT 1疫苗联合治疗中生存的有用预后标志物。进一步的临床研究是必要的，以确定这种联合治疗的有效性。
Supplemental Digital Content is available in the text. Wilms tumor gene (WT1) protein is an attractive target for cancer immunotherapy. We aimed to investigate the feasibility of a combination therapy consisting of gemcitabine and WT1 peptide–based vaccine for patients with advanced pancreatic cancer and to make initial assessments of its clinical efficacy and immunologic response. Thirty-two HLA-A*24:02+ patients with advanced pancreatic cancer were enrolled. Patients received HLA-A*24:02-restricted, modified 9-mer WT1 peptide (3 mg/body) emulsified with Montanide ISA51 adjuvant (WT1 vaccine) intradermally biweekly and gemcitabine (1000 mg/m2) on days 1, 8, and 15 of a 28-day cycle. This combination therapy was well tolerated. The frequencies of grade 3–4 adverse events for this combination therapy were similar to those for gemcitabine alone. Objective response rate was 20.0% (6/30 evaluable patients). Median survival time and 1-year survival rate were 8.1 months and 29%, respectively. The association between longer survival and positive delayed-type hypersensitivity to WT1 peptide was statistically significant, and longer survivors featured a higher frequency of memory-phenotype WT1-specific cytotoxic T lymphocytes both before and after treatment. WT1 vaccine in combination with gemcitabine was well tolerated for patients with advanced pancreatic cancer. Delayed-type hypersensitivity-positivity to WT1 peptide and a higher frequency of memory-phenotype WT1-specific cytotoxic T lymphocytes could be useful prognostic markers for survival in the combination therapy with gemcitabine and WT1 vaccine. Further clinical investigation is warranted to determine the effectiveness of this combination therapy.