Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.
Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.
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DOI：
10.1002/ijc.30182
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发表时间：
2016-09-15
影响因子：
6.4
通讯作者：
Sugiyama, Haruo
中科院分区：
文献类型：
--
作者：
Oji, Yusuke;Hashimoto, Naoya;Tsuboi, Akihiro;Murakami, Yui;Iwai, Miki;Kagawa, Naoki;Chiba, Yasuyoshi;Izumoto, Shuichi;Elisseeva, Olga;Ichinohasama, Ryo;Sakamoto, Junichi;Morita, Satoshi;Nakajima, Hiroko;Takashima, Satoshi;Nakae, Yoshiki;Nakata, Jun;Kawakami, Manabu;Nishida, Sumiyuki;Hosen, Naoki;Fujiki, Fumihiro;Morimoto, Soyoko;Adachi, Mayuko;Iwamoto, Masahiro;Oka, Yoshihiro;Yoshimine, Toshiki;Sugiyama, Haruo
我们先前在大量白血病或实体瘤患者中评估了肾母细胞瘤基因1（WT1）肽疫苗接种情况，并报道了HLA - A*24:02限制性的9聚体WT1 - 235肽（CYTWNQMNL）疫苗可诱导细胞免疫应答，并激发WT1 - 235特异性细胞毒性T淋巴细胞（CTLs）。然而，该疫苗是否诱导体液免疫应答以产生WT1抗体仍不清楚。因此，我们测量了接受WT1肽疫苗的多形性胶质母细胞瘤（GBM）患者中针对WT1 - 235肽的IgG抗体水平（WT1 - 235 IgG抗体）。在接种疫苗前无法检测到的WT1 - 235 IgG抗体，在59名患者中的30名（50.8%）患者接种WT1肽疫苗3个月期间可被检测到。主要的WT1 - 235 IgG抗体亚类为Th1型的IgG1和IgG3。WT1 - 235 IgG抗体的产生与无进展生存期（PFS）和总生存期（OS）均呈显著正相关。重要的是，WT1 - 235 IgG抗体产生与对WT1 - 235肽的迟发型超敏反应（DTH）阳性相结合，作为长期总生存期的预后标志物比单独的任一参数更好。这些结果表明，WT1 - 235肽疫苗接种不仅如先前所述诱导WT1 - 235特异性CTLs，还诱导与抗肿瘤细胞免疫应答相关的WT1 - 235特异性体液免疫应答。我们的结果表明，针对WT1肽的WT1 IgG抗体可能是一个有用的预测标志物，与对WT1肽的DTH相结合具有更好的预测性能，并为WT1肽疫苗治疗患者的抗肿瘤免疫应答诱导提供了新的见解。
有什么新发现？
肾母细胞瘤基因1（WT1）抗原是针对多形性胶质母细胞瘤（GBM）这种生存率低的脑肿瘤的免疫治疗策略的一个有前景的靶点。本研究表明，WT1 - 235肽疫苗接种可在GBM患者中诱导WT1 - 235特异性体液免疫应答。WT1 - 235 IgG抗体的产生与无进展生存期和总生存期的延长显著相关。对WT1肽呈迟发型超敏反应（DTH）阳性的GBM患者的生存期明显更长。因此，在接受WT1疫苗治疗的GBM患者中，特别是那些表现出DTH阳性反应的患者，WT1 - 235 IgG抗体的产生可预测长期生存期。
We previously evaluated Wilms’ tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA‐A*24:02 restricted, 9‐mer WT1‐235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1‐235‐specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1‐235 peptide (WT1‐235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1‐235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1‐235 IgG antibody subclass was Th1‐type, IgG1 and IgG3. WT1‐235 IgG antibody production was significantly and positively correlated with both progression‐free survival (PFS) and overall survival (OS). Importantly, the combination of WT1‐235 IgG antibody production and positive delayed type‐hypersensitivity (DTH) to the WT1‐235 peptide was a better prognostic marker for long‐term OS than either parameter alone. These results suggested that WT1‐235 peptide vaccination induces not only WT1‐235‐specific CTLs as previously described but also WT1‐235‐specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine‐treated patients. What's new? The Wilms' tumor gene 1 (WT1) antigen is a promising target for immunotherapeutic strategies against glioblastoma multiforme (GBM), a brain tumor with poor survival rates. The present study shows that vaccination with WT1‐235 peptide can induce WT1‐235‐specific humoral immune responses in GBM patients. WT1‐235 IgG antibody production was significantly associated with prolonged progression‐free survival and overall survival. Survival times were significantly longer in GBM patients with positive delayed‐type hypersensitivity (DTH) responses to WT1 peptide. Thus, in WT1 vaccine‐treated GBM patients, especially those exhibiting positive DTH responses, WT1‐235 IgG antibody production can predict long‐term survival.
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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：
4.1
作者：
Izumoto, Shuichi;Tsuboi, Akihiro;Yosihmine, Toshiki
通讯作者：
Yosihmine, Toshiki
影响因子：
20.3
作者：
Gao, LQ;Bellantuono, I;Stauss, HJ
通讯作者：
Stauss, HJ
影响因子：
45.3
作者：
Gilbert, Mark R.;Wang, Meihua;Mehta, Minesh P.
通讯作者：
Mehta, Minesh P.
影响因子：
64.5
作者：
CALL, KM;GLASER, T;HOUSMAN, DE
通讯作者：
HOUSMAN, DE