A panel of human variable heavy (VH) single domain monoclonal antibodies specific for cell-surface glypican-2 (GPC2) are described. Methods for the diagnosis and treatment and GPC2-positive cancer are also described. Recombinant immunotoxins comprised of a GPC2-specific VH domain antibody and a clinically used form of Pseudomonas exotoxin A (PE38) were generated and shown to inhibit GPC2-positive neuroblastoma tumor cell growth and inhibit neuroblastoma xenograft growth in nude mice, without significant toxicity. Chimeric antigen receptors comprising a GPC2-specific VH single domain antibody are also described. T cells expressing the GPC2-specific CARs potently killed GPC2-positive neuroblastoma cells in a dose-dependent manner.
本文描述了一组特异于细胞表面糖蛋白-2(
GPC2)的人类可变重型(
VH)单克隆
抗体。还介绍了诊断和治疗
GPC2 阳性癌症的方法。由
GPC2 特异性
VH 结构域
抗体和临床上常用的假单胞菌外毒素 A(PE38)组成的
重组免疫毒素已经产生,并证明可抑制
GPC2 阳性神经母细胞瘤肿瘤细胞的生长和抑制神经母细胞瘤异种移植在裸鼠体内的生长,且无明显毒性。此外,还介绍了由
GPC2 特异性
VH 单结构域
抗体组成的嵌合抗原受体。表达
GPC2 特异性 CAR 的 T 细胞能以剂量依赖的方式有效杀死
GPC2 阳性的神经母细胞瘤细胞。