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首页> 外文期刊>Journal of Immunological Methods >A subtraction tolerization method of immunization allowed for Wilms' tumor protein-1 (WT1) identification in melanoma and discovery of an antitumor peptide sequence
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A subtraction tolerization method of immunization allowed for Wilms' tumor protein-1 (WT1) identification in melanoma and discovery of an antitumor peptide sequence

机译：免疫的减法耐受方法可用于在黑素瘤中鉴定Wilms的肿瘤蛋白1（WT1）和发现抗肿瘤肽序列

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摘要

On searching for melanoma transcription factors in a project focusing on internal antitumor peptide sequences from transcription factors, we found that a highly immunogenic component emerged upon using a subtraction tolerization method of immunization. While several conventional immunization procedures using whole melanoma cells induced a plethora of low affinity antibodies of various specificities, the subtraction tolerization method efficiently elicited mono-specific antibodies that recognized Wilms' tumor protein 1 (WT1), which is known as an important marker in melanoma prognosis and treatment For the tolerization step, pre-immunization of Balb/c mice with a membrane-rich preparation of glioblastoma U87 cells was used. The subsequent immunizations with SK-MEL-28 melanoma cells elicited antibodies strongly reacting with 50 and 55 kDa proteins, identified as WT1. Remarkably, this was the only component strongly reactive with these antibodies in a melanoma cell lysate. WT1 was then chosen as a target for selecting internally bioactive peptides. A hydrophilic Trojan peptide containing most of the zinc finger-2 domain of WT1 was synthesized and shown to inhibit SK-MEL-28 melanoma growth in vitro. The peptide WT1-pTj was also protective in vivo in a metastatic melanoma model and peptide-stimulated syngeneic dendritic cells reproduced the anti-melanoma effect of the unprotected peptide. Identification of antitumor peptides derived from major transcription factors represents a new tool to be explored in cancer research aiming at new therapeutic drugs. (C) 2014 Elsevier B.V. All rights reserved.
机译：在从一个转录因子着眼于内部抗肿瘤肽序列的项目中寻找黑素瘤转录因子时，我们发现在使用减法耐受免疫方法后出现了高度免疫原性的成分。尽管使用全黑素瘤细胞的几种常规免疫程序可诱导大量各种特异性的低亲和力抗体，但是减法耐受方法有效地诱导了识别威尔姆斯肿瘤蛋白1（WT1）的单特异性抗体，该蛋白被认为是黑素瘤中的重要标志物预后和治疗在耐受步骤中，使用富含膜的胶质母细胞瘤U87细胞预免疫Balb / c小鼠。随后用SK-MEL-28黑色素瘤细胞进行免疫接种，产生了与50和55 kDa蛋白强烈反应的抗体，这些蛋白被鉴定为WT1。值得注意的是，这是在黑色素瘤细胞裂解物中与这些抗体发生强烈反应的唯一成分。然后选择WT1作为选择内部生物活性肽的靶标。合成了一种亲水的Trojan肽，该蛋白包含WT1的大部分锌指2结构域，并显示出在体外抑制SK-MEL-28黑色素瘤的生长。 WT1-pTj肽在转移性黑素瘤模型中也具有体内保护作用，而肽刺激的同系树突细胞可复制未保护肽的抗黑素瘤作用。源自主要转录因子的抗肿瘤肽的鉴定代表了针对新治疗药物的癌症研究中将探索的新工具。 （C）2014 Elsevier B.V.保留所有权利。

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