WT1 epitope-specific IgG and IgM antibodies for immune-monitoring in patients with advanced sarcoma treated with a WT1 peptide cancer vaccine.
WT1 epitope-specific IgG and IgM antibodies for immune-monitoring in patients with advanced sarcoma treated with a WT1 peptide cancer vaccine.
复制标题
DOI：
10.3892/ol.2022.13184
复制
发表时间：
2022-03
期刊：
影响因子：
2.9
通讯作者：
Oji Y
中科院分区：
文献类型：
--
作者：
Alzaaqi S;Naka N;Hamada K;Hosen N;Kanegae M;Outani H;Adachi M;Imanishi R;Morii E;Iwai M;Nakata J;Fujiki F;Morimoto S;Nakajima H;Nishida S;Tsuboi A;Oka Y;Sugiyama H;Oji Y
Wilms'肿瘤基因WT 1在多种恶性肿瘤中高表达，可能是肿瘤免疫治疗的共同靶抗原。在我们的小组中，开发了针对WT 1 CTL表位的基于肽的癌症疫苗作为这些恶性肿瘤的免疫疗法。在本研究中，WT 1表位特异性免疫反应进行了分析，在31例晚期肉瘤与人类白细胞抗原-A *24：02-和WT 1表达肿瘤谁收到WT 1 -235肽疫苗作为单一疗法。使用ELISA测量针对靶表位WT 1 -235和非靶表位WT 1 -332和WT 1 -271的IgG和IgM抗体的血清水平。在疫苗接种前，分别在3例（9.6%）、4例（12.9%）和20例（64.5%）患者中检测到针对WT 1 -235、WT 1 -332和WT 1 -271的IgM抗体，表明在疫苗接种前对WT 1抗原进行了免疫识别。在完成3个月治疗方案的15例患者中，5例（33.3%）患者的WT 1 -235 IgG呈阳性。酶联免疫斑点试验显示，在接种疫苗开始时WT 1 - 235 IgM阳性的所有3例患者中，外周血单核细胞中WT 1 - 235表位特异性IL-10的产生/分泌在接种疫苗的第一个月下降。此外，治疗开始时WT 1 -235和WT 1 -271 IgM抗体阳性与疫苗接种后3个月的不利肿瘤控制相关。这些结果表明，WT 1表位特异性IgG和IgM抗体可用作WT 1肽癌症疫苗免疫治疗的免疫监测标志物。这些试验已录入大学医院医学信息网络（UMIN）临床试验登记处（2009年5月24日编号UMIN 00002001，2014年12月20日编号UMIN 000015997）。
The Wilms' tumor gene WT1 is highly expressed in various malignancies and may be a common target antigen for cancer immunotherapy. In our group, peptide-based cancer vaccines targeting WT1 CTL epitopes were developed as an immunotherapy for these malignancies. In the present study, WT1 epitope-specific immune responses were analyzed in 31 patients with advanced sarcoma with human leukocyte antigen-A*24:02- and WT1-expressing tumors who received the WT1-235 peptide vaccine as monotherapy. The serum levels of IgG and IgM antibodies against the target epitope WT1-235 and the non-target epitopes WT1-332 and WT1-271 were measured using ELISA. IgM antibodies against WT1-235, WT1-332 and WT1-271 were detected in three (9.6%), four (12.9%) and 20 patients (64.5%), respectively, prior to vaccine administration, indicating immune recognition of the WT1 antigen prior to administering the vaccine. Of 15 patients who had completed the 3-month treatment protocol, WT1-235 IgG was positive in five (33.3%) patients. An enzyme-linked immunospot assay revealed that WT1-235 epitope-specific IL-10 production/secretion in peripheral blood mononuclear cells declined in the first month of vaccine administration in all three patients with positivity for WT1-235 IgM at the start of the vaccine. Furthermore, positivity for both WT1-235 and WT1-271 IgM antibodies at the start of treatment was associated with unfavorable tumor control at 3 months after vaccine administration. These results suggested that WT1 epitope-specific IgG and IgM antibodies may be utilized as immune-monitoring markers for WT1 peptide cancer vaccine immunotherapy. The trials were entered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry (; no. UMIN000002001 on May 24, 2009 and no. UMIN000015997 on December 20, 2014).
登录
查看更多内容
影响因子：
7.5
作者：
Maslak, Peter G.;Dao, Tao;Scheinberg, David A.
通讯作者：
Scheinberg, David A.
影响因子：
5.7
作者：
Oji, Y;Yamamoto, H;Sugiyama, H
通讯作者：
Sugiyama, H
影响因子：
7.5
作者：
Nakatsuka, S;Oji, Y;Aozasa, K
通讯作者：
Aozasa, K
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：
Keilholz, Ulrich;Letsch, Anne;Scheibenbogen, Carmen
通讯作者：
Scheibenbogen, Carmen