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.
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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来自接受 Globo H 匙孔血蓝蛋白疫苗免疫的患者的多克隆抗体：通过使用完全合成的固定化肿瘤抗原来分离、定量和表征免疫反应。
DOI：
10.1073/pnas.97.6.2719
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发表时间：
2000
影响因子：
11.1
通讯作者：
Danishefsky,SJ
中科院分区：
文献类型：
--
作者：
Wang,ZG;Williams,LJ;Zhang,XF;Zatorski,A;Kudryashov,V;Ragupathi,G;Spassova,M;Bornmann,W;Slovin,SF;Scher,HI;Livingston,PO;Lloyd,KO;Danishefsky,SJ
我们之前已经报道了一种基于碳水化合物的疫苗计划，用于癌症患者的免疫治疗。一种基于Globo H抗原与锁孔血蓝蛋白(KLH)偶联的疫苗已进入临床评估阶段。虽然这种碳水化合物疫苗和其他碳水化合物疫苗已经被证明可以诱导抗体反应，但目前还没有关于这些或其他抗癌疫苗在免疫患者中达到的抗体水平的定量数据。我们在此报告了一种连接到亲和矩阵上的复杂合成寡糖的有效方法，用于鉴定和分离针对这种基于碳水化合物的疫苗在人类中产生的抗体。比较了用Globo H-KLH免疫的患者接种前后的血清标本的变化情况。所有抗Globo H抗体活性均与其他血清成分有效分离。分离的抗体很容易被量化，并分析它们的特异性。由于没有其他癌症患者接种疫苗产生的抗体的可比数据，我们将观察到的水平与已量化的细菌多糖疫苗研究中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抗体水平往往超过用细菌多糖免疫形成的抗体水平。此外，大量的免疫球蛋白抗体和免疫球蛋白M抗体都被激发出来，这清楚地表明了一种向免疫球蛋白的转变。综上所述，这些分析有助于澄清疫苗免疫反应的几个方面，并为基于碳水化合物的疫苗接种策略提供几个新的见解。此外，如此分离的抗体很可能在临床治疗中应用。
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 complex synthetic oligosaccharides attached to an affinity matrix for identifying and isolating antibodies elicited against such a carbohydrate-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 separated 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 observed levels with those quoted in studies with bacterial polysaccharide vaccines that had been quantified. Remarkably, cancer patients immunized with globo H-KLH produce anti-globo H antibody 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 IgG. 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 strategy. Furthermore, antibodies so isolated could well have applications in clinical therapy.
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DOI：
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发表时间：
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