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一种针对白色念珠菌应激甘露糖蛋白的单克隆抗体的抗真菌和抗肿瘤活性

Antifungal and antitumor activities of a monoclonal antibody directed against a stress mannoprotein of Candida albicans.

作者信息

Omaetxebarría M J, Moragues M D, Elguezabal N, Rodríguez-Alejandre A, Brena S, Schneider J, Polonelli L, Pontón J

机构信息

Departamento de Inmunología, Microbiología y Parasitología, Facultad de Medicina y Odontología, Universidad del País Vasco, Bilbao, Vizcaya, Spain.

出版信息

Curr Mol Med. 2005 Jun;5(4):393-401. doi: 10.2174/1566524054022521.

Abstract

Immunization of mice with a stress mannoprotein of >200 kDa from the cell wall of Candida albicans led to the production of monoclonal antibody (Mab) C7. The immunogen is a major target of secretory IgA and its expression is regulated by different environmental conditions including temperature, pH, glucose concentration and ammonium sulphate in the culture medium. Mab C7 reacted with a peptide epitope present in the >200 kDa antigen as well as in a number of antigens from the blastoconidium and germ tube cell wall, including enolase. In addition to its reactivity with C. albicans, Mab C7 also reacted with antigens present in C. krusei, C, tropicalis, C. glabrata, C. dubliniensis and C. lusitaniae, as well as in Cryptococcus neoformans, Scedosporium prolificans and Aspergillus fumigatus. Mab C7 exhibited four important biological activities, namely inhibition of adhesion of C. albicans to a variety of surfaces, inhibition of germination of C. albicans, direct candidacidal activity and direct tumoricidal activity. In tumor cells, Mab C7 reacted with nucleoporin Nup88, a reactivity that can be utilized for diagnostic and prognostic purposes.

摘要

用白色念珠菌细胞壁中大于200 kDa的应激甘露糖蛋白免疫小鼠,可产生单克隆抗体(Mab)C7。该免疫原是分泌型IgA的主要靶点,其表达受不同环境条件调控,包括温度、pH值、葡萄糖浓度和培养基中的硫酸铵。Mab C7与大于200 kDa抗原以及许多来自芽生孢子和芽管细胞壁的抗原(包括烯醇化酶)中存在的肽表位发生反应。除了与白色念珠菌发生反应外,Mab C7还与克鲁斯念珠菌、热带念珠菌、光滑念珠菌、都柏林念珠菌和葡萄牙念珠菌以及新型隐球菌、多育赛多孢和烟曲霉中存在的抗原发生反应。Mab C7表现出四种重要的生物学活性,即抑制白色念珠菌对多种表面的黏附、抑制白色念珠菌的萌发、直接杀念珠菌活性和直接杀肿瘤活性。在肿瘤细胞中,Mab C7与核孔蛋白Nup88发生反应,这种反应性可用于诊断和预后目的。

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