Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer.
Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer.
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DOI：
10.1111/cas.12621
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发表时间：
2015-04
期刊：
影响因子：
5.7
通讯作者：
Kitagawa Y
中科院分区：
文献类型：
--
作者：
Mayanagi S;Kitago M;Sakurai T;Matsuda T;Fujita T;Higuchi H;Taguchi J;Takeuchi H;Itano O;Aiura K;Hamamoto Y;Takaishi H;Okamoto M;Sunamura M;Kawakami Y;Kitagawa Y
本研究旨在评价Wilms肿瘤基因1(WT1)多肽冲击的树突状细胞疫苗联合吉西他滨(DCGEM)作为一线治疗晚期胰腺癌的可行性和免疫应答。10例HLAA2402患者分别于第8、22天接受WT1多肽冲击的DC疫苗(1×10~7细胞)和吉西他滨(1000 mg/m2)第1、8、15天的治疗。采用迟发型变态反应皮肤试验、干扰素-γ酶联免疫斑点试验和HLA四聚体试验以及各种免疫学因子的检测来评价WT1特异性免疫应答的诱导。DCGEM耐受性良好，吉西他滨的相对剂量强度为87%。3例迟发型超敏反应阳性患者均可观察到中性粒细胞/淋巴细胞比值低的疾病控制情况，也与治疗前外周血粒细胞髓系抑制细胞比例低有关(P<0.017)。肝转移和炎症标记物如C-反应蛋白和白介素8(IL-8)水平高的患者，即使诱导了WT1特异性免疫反应，存活率也很低。WT1多肽冲击的DCGEM诱导抗肿瘤T细胞反应是可行和有效的。我们的结果支持了未来对无肝转移且免疫学状况良好的胰腺癌患者的研究。这项试验在大学医院医学信息网(UMIN)临床试验登记处注册(http://www.umin.ac.jp/ctr/编号：UMIN-000004855)。
This study aimed to evaluate the feasibility of and immune response to Wilms tumor gene 1 (WT1) peptide-pulsed dendritic cell vaccination combined with gemcitabine (DCGEM) as a first-line therapy among patients with advanced pancreatic cancer. Ten HLA-A*2402 patients were treated with WT1 peptide-pulsed DC vaccination (1 × 107 cells) on days 8 and 22 and gemcitabine (1000 mg/m2) on days 1, 8 and 15. Induction of a WT1-specific immune response was evaluated using the delayed-type hypersensitivity (DTH) skin test, interferon-γ enzyme-linked immunospot and HLA tetramer assays, along with assays for various immunological factors. DCGEM was well-tolerated, and the relative dose intensity of gemcitabine was 87%. Disease control associated with a low neutrophil/lymphocyte ratio was observed in all three patients with DTH positivity; it was also correlated with a low percentage of granulocytic myeloid derived suppressor cells in the pretreatment peripheral blood (P = 0.017). Patients with liver metastases and high levels of inflammatory markers such as C-reactive protein and interleukin-8 (IL-8) showed poor survival even though a WT1-specific immune response was induced in them. WT1 peptide-pulsed DCGEM is feasible and effective for inducing anti-tumor T-cell responses. Our results support future investigations for pancreatic cancer patients with non-liver metastases and favorable immunological conditions. This trial was registered with the University hospital Medical Information Network (UMIN) Clinical Trials Registry (http://www.umin.ac.jp/ctr/ number: UMIN-000004855).
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1097/cji.0000000000000020
发表时间：
2014-02
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
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
通讯作者：
Sugiyama H
影响因子：
64.5
作者：
CALL, KM;GLASER, T;HOUSMAN, DE
通讯作者：
HOUSMAN, DE
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.