Leung Kam
National Center for Biotechnology Information, NLM, NIH
Disialoganglioside GD2 is a glycolipid on cell surfaces of neurons that involves cell–matrix interactions (1). GD2 is highly expressed on tumors of neuroectodermal origin, such as neuroblastoma and melanoma cells, whereas GD2 is weakly expressed on most normal cells (2). Therefore, GD2 is a useful target for both identification and treatment of tumor cells with monoclonal antibodies (mAbs), such as chimeric mAb ch14.18 and humanized mAb hu14.18 (3, 4). Both mAbs are now in clinical trials for treatment of melanoma and neuroblastoma. hu14.18K322A, a variant of hu14.18 with a single-spot mutation, was developed to decrease complement activation to minimize cytotoxic side effects of ch14.18 and hu14.18 (5). Vavere et al. (6) evaluated Cu-1,4,7,10-tetraazacyclododecane-,','','''-tetraacetic acid--benzyl-NH-hu14.18K322A (Cu-DOTA-Bn-NH-hu14.18K322A) for use with positron emission tomography (PET) imaging of GD2 expression in nude mice bearing human tumors.
双唾液酸神经节苷脂GD2是神经元细胞表面的一种糖脂，参与细胞与基质的相互作用（1）。GD2在神经外胚层来源的肿瘤细胞表面高表达，如神经母细胞瘤和黑色素瘤细胞，而在大多数正常细胞上弱表达（2）。因此，GD2是用单克隆抗体（mAb）识别和治疗肿瘤细胞的有用靶点，如嵌合单克隆抗体ch14.18和人源化单克隆抗体hu14.18（3,4）。这两种单克隆抗体目前都在进行治疗黑色素瘤和神经母细胞瘤的临床试验。hu14.18K322A是hu14.18的一个单点突变变体，旨在减少补体激活，以尽量减少ch14.18和hu14.18的细胞毒性副作用（5）。Vavere等人（6）评估了铜-1,4,7,10-四氮杂环十二烷-N,N,N',N'-四乙酸-苄基-NH-hu14.18K322A（Cu-DOTA-Bn-NH-hu14.18K322A）用于对携带人肿瘤的裸鼠进行GD2表达的正电子发射断层扫描（PET）成像。
