对病毒抗原具有交叉反应性的肿瘤结合抗体。

IF 5.1 2区 医学 Q2 IMMUNOLOGY
Michael J Campa, Elizabeth B Gottlin, Kevin Wiehe, Edward F Patz
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引用次数: 0

摘要

背景:我们之前在非小细胞肺癌(NSCLC)患者中发现了一种补体因子H (CFH)自身抗体,该抗体与I期疾病患者的非转移性疾病和更长的进展时间相关。从患者体内分离的单个B细胞中克隆出重组人抗体GT103。GT103抑制肿瘤生长,建立抗肿瘤微环境。抗CFH自身抗体和GT103识别CFH SCR19结构域内的表位PIDNGDIT。在这里,我们询问这种自身抗体是否最初是作为对先前感染的病毒蛋白中类似表位的体液反应而产生的。方法:鉴定合成与PIDNGDIT核心表位序列序列高度同源的病毒肽。采用ELISA法检测非小细胞肺癌患者血浆中抗cfh自身抗体。GT103在4345肽病原体芯片上进行检测。结果:与GT103表位相似的表位存在于几种病毒中,包括人偏肺病毒-1 (HMPV-1),其在附着糖蛋白G中包含一个序列,其差异为一个氨基酸。非小细胞肺癌患者血浆中的抗cfh自身抗体与含有表位的HMPV-1肽弱结合。GT103与多肽芯片上的多个病毒表位交叉反应,最上面的是人内源性逆转录病毒- k聚合酶(HERV-K pol)蛋白和麻疹血凝素糖蛋白中的肽。GT103结合病毒HMPV-1、HERV-K pol和麻疹表位肽,但与GT103表位肽相比,其亲和力较低。结论:这些发现表明,针对病毒靶点的记忆B细胞可能具有亲和力成熟,从而产生识别肿瘤细胞上相似表位的抗体,并具有抗肿瘤特性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A tumor-binding antibody with cross-reactivity to viral antigens.

A tumor-binding antibody with cross-reactivity to viral antigens.

A tumor-binding antibody with cross-reactivity to viral antigens.

A tumor-binding antibody with cross-reactivity to viral antigens.

Background: We previously identified in non-small cell lung cancer (NSCLC) patients an autoantibody to complement factor H (CFH) that is associated with non-metastatic disease and longer time to progression in patients with stage I disease. A recombinant human antibody, GT103, was cloned from single B cells isolated from patients with the autoantibody. GT103 inhibits tumor growth and establishes an antitumor microenvironment. The anti-CFH autoantibody and GT103 recognize the epitope PIDNGDIT within the SCR19 domain of CFH. Here, we asked if this autoantibody could have originally arisen as a humoral response to a similar epitope in a viral protein from a prior infection.

Methods: Homologous viral peptides with high sequence identity to the core PIDNGDIT epitope sequence were identified and synthesized. NSCLC patient plasma containing anti-CFH autoantibodies were assayed by ELISA against these peptides. GT103 was assayed on a 4345-peptide pathogen microarray.

Results: Epitopes similar to the GT103 epitope are present in several viruses, including human metapneumovirus-1 (HMPV-1) that contains a sequence within attachment glycoprotein G that differs by one amino acid. Anti-CFH autoantibodies in NSCLC patient plasma weakly bound to an HMPV-1 peptide containing the epitope. GT103 cross-reacted with multiple viral epitopes on a peptide microarray, with the top hits being peptides in the human endogenous retrovirus-K polymerase (HERV-K pol) protein and measles hemagglutinin glycoprotein. GT103 bound the viral HMPV-1, HERV-K pol, and measles epitope peptides but with lower affinity compared to the GT103 epitope peptide.

Conclusion: These findings suggest that memory B cells against a viral target could have affinity matured to produce an antibody that recognizes a similar epitope on tumor cells and exhibits antitumor properties.

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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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