Yin Zhaojun, Dulaney Steven, McKay Craig S, Baniel Claire, Kaczanowska Katarzyna, Ramadan Sherif, Finn M G, Huang Xuefei
Department of Chemistry, Michigan State University, 578 S. Shaw Lane, Room 426, East Lansing, MI, 48824-1322, USA.
School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332-0400, USA.
Chembiochem. 2016 Jan;17(2):174-80. doi: 10.1002/cbic.201500499. Epub 2015 Dec 4.
The development of carbohydrate-based antitumor vaccines is an attractive approach towards tumor prevention and treatment. Herein, we focused on the ganglioside GM2 tumor-associated carbohydrate antigen (TACA), which is overexpressed in a wide range of tumor cells. GM2 was synthesized chemically and conjugated with a virus-like particle derived from bacteriophage Qβ. Although the copper-catalyzed azide-alkyne cycloaddition reaction efficiently introduced 237 copies of GM2 per Qβ, this construct failed to induce significant amounts of anti-GM2 antibodies compared to the Qβ control. In contrast, GM2 immobilized on Qβ through a thiourea linker elicited high titers of IgG antibodies that recognized GM2-positive tumor cells and effectively induced cell lysis through complement-mediated cytotoxicity. Thus, bacteriophage Qβ is a suitable platform to boost antibody responses towards GM2, a representative member of an important class of TACA: the ganglioside.
基于碳水化合物的抗肿瘤疫苗的开发是一种有吸引力的肿瘤预防和治疗方法。在此，我们聚焦于神经节苷脂GM2肿瘤相关碳水化合物抗原（TACA），其在多种肿瘤细胞中过表达。GM2通过化学合成，并与源自噬菌体Qβ的病毒样颗粒偶联。尽管铜催化的叠氮化物-炔烃环加成反应在每个Qβ上高效引入了237个GM2拷贝，但与Qβ对照相比，该构建体未能诱导产生大量的抗GM2抗体。相反，通过硫脲接头固定在Qβ上的GM2引发了高滴度的IgG抗体，这些抗体识别GM2阳性肿瘤细胞，并通过补体介导的细胞毒性有效诱导细胞裂解。因此，噬菌体Qβ是增强针对GM2（一种重要类型的TACA——神经节苷脂的代表性成员）的抗体反应的合适平台。
