BACKGROUND:Gangliosicle GD2 is abundant on human neuroblastoma (NB). Monoclonal antibody 3F8 targeted to GD2 may have imaging and therapeutic potential. Antigen-negative clones can escape immune-mediated attack leading to clinical resistance or recurrence. PROCEDURE:Among 95 evaluable patients treated intravenously with 3F8 (94 Stage 4, 1 Stage 3), 66 received nonradiolabeled 3F8, 11 received 131-iodine-labeled-3F8 (8-28 mCi/kg) with autologous bone marrow rescue, and 18 received both forms of treatment. Prior to treatment, 90 patients tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 68), tumor immunohistochemistry (n = 20), or diagnostic radioimmunoscintigraphy (n = 2). RESULTS:Of 62 patients who had refractory or recurrent neuroblastoma following 3F8 treatment, 61 (98%) tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 51) or tumor immunohistochemistry (n = 10). The sole tumor that lost GD2 expression underwent phenotypic transformation into a pheochromocytoma-like tumor. CONCLUSIONS:The persistence of GD2 expression in refractory or recurrent NB suggests that complete antigen loss is an uncommon event and cannot account for treatment failure.

译文

背景:神经节GD2在人神经母细胞瘤(NB)中含量丰富。靶向GD2的单克隆抗体3F8可能具有成像和治疗潜力。抗原阴性克隆可以逃脱免疫介导的攻击,从而导致临床耐药或复发。
程序:在95例可评估的患者中,静脉注射3F8(94阶段4,1阶段3),66例接受了非放射性标记的3F8,11例接受了131碘标记的3F8(8-28 mCi / kg)的自体骨髓拯救术,18例接受了两种形式的治疗。在治疗之前,有90名患者通过骨髓免疫荧光检查(n = 68),肿瘤免疫组织化学检查(n = 20)或诊断性放射免疫闪烁照相术(n = 2)检测出GD2反应阳性。
结果:62例3F8治疗后患有难治性或复发性神经母细胞瘤的患者中,有61例(98%)通过骨髓免疫荧光(n = 51)或肿瘤免疫组织化学(n = 10)检测为GD2反应阳性。唯一丢失GD2表达的肿瘤发生了表型转化为嗜铬细胞瘤样肿瘤。
结论:难治性或复发性NB中GD2表达的持续性提示完全抗原丢失是罕见的事件,不能解释治疗失败的原因。

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