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基于糖芯片评估人抗血蓝蛋白抗体反应。

Evaluation of human antibody responses to keyhole limpet hemocyanin on a carbohydrate microarray.

机构信息

Laboratory of Medicinal Chemistry, National Cancer Institute, Frederick, MD, USA.

出版信息

Proteomics Clin Appl. 2010 Mar;4(3):285-94. doi: 10.1002/prca.200900130. Epub 2010 Feb 11.

Abstract

PURPOSE

Keyhole limpet hemocyanin (KLH) is used as a vaccine adjuvant, as a carrier protein for small haptens, and as a treatment for bladder cancer. Immunization with KLH produces antibodies to tumor-associated carbohydrate antigens (TACAs) in animals, and these antibodies have been postulated as the basis of efficacy for bladder cancer treatment. The purpose of this study was to evaluate antibody responses to KLH in humans.

EXPERIMENTAL DESIGN

A carbohydrate microarray was used to profile antibody responses in 14 individuals immunized with KLH plus alum adjuvant.

RESULTS

Eight out of fourteen individuals produced antibodies to at least one TACA. Increases to Lewis X, Lewis Y, GA1di, GM3, and sialyl Lewis A were observed in certain individuals, but, in general, antibody profiles were highly variable. Pre-immunization antibody levels to a subset of array antigens had a statistically significant correlation with the magnitude of the antibody response to KLH.

CONCLUSIONS AND CLINICAL RELEVANCE

Antibodies to TACAs can be produced in humans, but antibody profiles differ considerably from person to person, which may contribute to variable clinical responses with KLH. Pre-treatment antibody levels to certain antigens may be useful for predicting which patients will respond favorably to KLH.

摘要

目的

豆科软体动物血蓝蛋白(KLH)被用作疫苗佐剂、小分子半抗原的载体蛋白以及膀胱癌的治疗药物。KLH 免疫可在动物体内产生针对肿瘤相关碳水化合物抗原(TACA)的抗体,这些抗体被认为是膀胱癌治疗效果的基础。本研究旨在评估 KLH 在人类中的抗体反应。

实验设计

使用碳水化合物微阵列分析 14 名接受 KLH 加铝佐剂免疫的个体的抗体反应。

结果

14 名个体中有 8 名至少产生了针对一种 TACA 的抗体。在某些个体中观察到 Lewis X、Lewis Y、GA1di、GM3 和唾液酸 Lewis A 的增加,但总体而言,抗体谱高度可变。数组抗原的亚组的预免疫抗体水平与对 KLH 的抗体反应的幅度具有统计学显著相关性。

结论和临床相关性

可以在人类中产生针对 TACA 的抗体,但抗体谱因人而异,这可能导致 KLH 的临床反应存在差异。对某些抗原的治疗前抗体水平可能有助于预测哪些患者对 KLH 反应良好。

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