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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Polyclonal antibodies from patients immunized with a globo H-keyhole limpet hemocyanin vaccine: Isolation, quantification, and characterization of immune responses by using totally synthetic immobilized tumor antigens
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Polyclonal antibodies from patients immunized with a globo H-keyhole limpet hemocyanin vaccine: Isolation, quantification, and characterization of immune responses by using totally synthetic immobilized tumor antigens

机译:来自使用球蛋白H匙孔戚血蓝蛋白疫苗免疫的患者的多克隆抗体:使用完全合成的固定化肿瘤抗原的免疫应答的分离,定量和表征

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We have previously reported on a carbohydrate-based vaccine program for immunotherapy in cancer patients. One such vaccine, based on the globo H antigen conjugated to the protein keyhole limpet hemocyanin (KLH), has been in clinical evaluation. Although this and other carbohydrate vaccines have been shown to induce antibody responses. there are currently no quantitative data on the antibody levels achieved in immunized patients by these or other anti-cancer vaccines. We report herein an efficient route to com- plex synthetic oligosaccharides attached to an affinity matrix for identifying and isolating antibodies elicited against such a carbo- hydrate-based vaccine in humans. Pre- and postvaccination profiles from serum samples of patients immunized with globo H-KLH were compared. All anti-globo H antibody activity was efficiently sep- arated from other serum constituents. The isolated antibodies were readily quantified, and their specificities were analyzed. Since no comparable data were available on antibodies resulting from the vaccination of other cancer patients, we compared the ob- served levels with those quoted in studies with bacterial polysac- charide vaccines that had been quantified. Remarkably, cancer patients immunized with globo H-KLH produce anti-globo H anti- body levels often exceeding those formed by immunization with bacterial polysaccharides. In addition. substantial quantities of both IgG and IgM antibodies were elicited. clearly indicating a class switch to lgG. Taken together, these analyses serve to clarify several aspects of the immune response to the vaccine and give several new insights to the carbohydrate-based vaccination strat- egy. Furthermore, antibodies so isolated could well have applica- tions in clinical therapy.
机译:我们先前已经报道了针对癌症患者进行免疫疗法的基于碳水化合物的疫苗计划。一种这样的疫苗已经在临床评估中,该疫苗基于与蛋白锁孔戚血蓝蛋白(KLH)缀合的球H抗原。尽管已证明这种和其他碳水化合物疫苗可诱导抗体反应。目前尚无关于这些或其他抗癌疫苗在免疫患者中获得的抗体水平的定量数据。我们在此报告了一种有效的方法,可以将复杂的合成寡糖与附着于亲和基质的复合物进行复合,以鉴定和分离针对人体中此类基于碳水化合物的疫苗的抗体。比较了用globo H-KLH免疫的患者血清样品的疫苗接种前后情况。所有抗球蛋白H抗体的活性均与其他血清成分有效分离。分离出的抗体易于定量,并分析其特异性。由于尚无其他癌症患者接种疫苗产生的抗体的可比数据,因此我们将观察到的水平与已量化细菌多糖疫苗研究中所引用的水平进行了比较。值得注意的是,用globo H-KLH免疫的癌症患者产生的抗globo H抗体水平经常超过用细菌多糖免疫形成的水平。此外。引起大量的IgG和IgM抗体。清楚地表明已将类切换到lgG。综上所述,这些分析有助于阐明疫苗免疫反应的几个方面,并对基于碳水化合物的疫苗接种策略提供一些新见解。此外,如此分离的抗体很可能在临床治疗中具有应用。

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