Lo-Man R, Bay S, Vichier-Guerre S, Dériaud E, Cantacuzène D, Leclerc C
Unité de Biologie des Régulations Immunitaires, Institut Pasteur, 75724 Paris, France.
Cancer Res. 1999 Apr 1;59(7):1520-4.
Aberrant glycosylation of mucins leads to the exposure of cryptic carbohydrate antigens at the surface of carcinoma cells, which, therefore, represent potent targets for anticancer therapeutic vaccines. To date, the development of immunogens to stimulate immune response to such saccharidic antigens is based on carbohydrate conjugation to carrier proteins. However, these traditional protein conjugates are poorly defined in chemical composition and structure. As an alternative, we synthesized a multiple antigenic O-linked glycopeptide (MAG) carrying the carbohydrate Tn antigen associated with a CD4+ T-cell epitope (MAG:Tn-PV). This fully synthetic immunogen is highly defined in composition and carries a high saccharidic epitope ratio over the entire molecule. The MAG:Tn-PV was able to induce anti-Tn IgG antibodies that recognize human tumor cell lines. A therapeutic immunization protocol performed with this fully synthetic immunogen increased the survival of tumor-bearing mice. Thus, the accurately defined and versatile MAG system represents an efficient strategy to induce carbohydrate-specific antitumor immune responses but may also be applicable to the prevention of infectious diseases, if it is based on bacterial oligosaccharides.
黏蛋白的异常糖基化会导致癌细胞表面隐蔽的碳水化合物抗原暴露，因此，这些抗原成为抗癌治疗性疫苗的有力靶点。迄今为止，用于刺激针对此类糖类抗原的免疫反应的免疫原开发基于碳水化合物与载体蛋白的偶联。然而，这些传统的蛋白偶联物在化学成分和结构上定义不明确。作为替代方案，我们合成了一种多重抗原O-连接糖肽（MAG），其携带与CD4+ T细胞表位相关的碳水化合物Tn抗原（MAG:Tn-PV）。这种完全合成的免疫原在组成上高度明确，并且在整个分子中具有高糖类表位比例。MAG:Tn-PV能够诱导识别人类肿瘤细胞系的抗Tn IgG抗体。用这种完全合成的免疫原进行的治疗性免疫方案提高了荷瘤小鼠的存活率。因此，精确界定且通用的MAG系统代表了一种诱导碳水化合物特异性抗肿瘤免疫反应的有效策略，但如果基于细菌寡糖，也可能适用于预防传染病。
