Cheung N K, Landmeier B, Neely J, Nelson A D, Abramowsky C, Ellery S, Adams R B, Miraldi F
J Natl Cancer Inst. 1986 Sep;77(3):739-45. doi: 10.1093/jnci/77.3.739.
The antibody 3F8, an IgG3 murine monoclonal antibody (MoAb) against disialoganglioside GD2, could target iodine-131 (131I) to established subcutaneous human neuroblastoma (NB) xenografts in BALB/c nude mice. 131I-radiolabeled MoAb (0.125-1 mCi) was injected iv. Tumor radioactivity over time was calculated from scintigraphy, and radiation dose to individual tumors was calculated. Tumor shrinkage occurred only with 131I-labeled 3F8, but not with nonradioactive 3F8 or radiolabeled irrelevant antibody. While the tumor of the control mice enlarged by tenfold, the treated tumor showed over 95% shrinkage by 12 days. Both the rate of shrinkage and duration of tumor response were dose dependent. Calculated doses of more than 10,000 rad could be achieved. Only those tumors that received more than 4,200 rad were completely ablated without recurrence. Recurrent tumors were not antigen negative or radioresistant. These results confirmed the prediction based on imaging studies that human NB xenografts could be effectively eradicated with the use of 131I-labeled MoAb 3F8 with tolerable toxicities.
抗体3F8是一种针对二唾液酸神经节苷脂GD2的IgG3鼠单克隆抗体(MoAb),可将碘-131(131I)靶向接种于BALB/c裸鼠体内已形成的人神经母细胞瘤(NB)皮下异种移植瘤。静脉注射131I放射性标记的单克隆抗体(0.125 - 1毫居里)。通过闪烁扫描计算随时间变化的肿瘤放射性,并计算各个肿瘤的辐射剂量。仅131I标记的3F8可使肿瘤缩小,而非放射性的3F8或放射性标记的无关抗体则无此效果。对照小鼠的肿瘤增大了10倍,而经治疗的肿瘤在12天时缩小了95%以上。肿瘤缩小速率和反应持续时间均呈剂量依赖性。可实现超过10,000拉德的计算剂量。只有那些接受超过4,200拉德的肿瘤被完全消融且无复发。复发性肿瘤并非抗原阴性或放射抗性。这些结果证实了基于影像学研究的预测,即使用131I标记的MoAb 3F8并伴有可耐受的毒性时,人NB异种移植瘤可被有效根除。