S. McQuarrie, G. Miller, Mavanur R. Suresh, John R. Mercer
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引用次数: 39
摘要
一种多步骤放射免疫治疗(RIT)方法,利用双特异性单克隆抗体(BsMAb)与90Y标记的生物素化长循环脂质体的组合,作为上皮性卵巢癌病的潜在辅助治疗进行了测试。具有抗ca 125和抗生物素表位的BsMAb与涂有生物素的聚乙二醇化脂质体一起使用,将细胞毒性放射性核素90Y递送到肿瘤部位。这种方法被用来克服与传统策略相关的一些主要障碍,特别是与传统的单克隆抗体(MAb)放射性核素递送相比,增加了传递到肿瘤部位的放射性量。根据我们的策略,靶向和治疗部分的顺序腹腔内给药为提高治疗比率提供了基础。我们在此报告了使用我们的RIT方法对移植了NIH:OVCAR-3 (CA 125+)人卵巢癌细胞系的Balb/c裸鼠模型进行体内治疗的结果。一项正在进行的肿瘤生长延迟/对照研究表明,在NIH:OVCAR-3细胞系的Balb/c小鼠腹腔内异种移植中,治疗组与对照组相比,肿瘤和腹水发展的发病明显延迟。
Preliminary Results of Nanopharmaceuticals Used in the Radioimmunotherapy of Ovarian Cancer
A multistep radioimmunotherapeutic (RIT) approach, exploiting the combination of a bispecific monoclonal antibody (BsMAb) with 90Y labelled biotinylated long-circulating liposomes was tested as a potential adjuvant treatment for epithelial ovarian carcinomatosis. The BsMAb, with anti-CA 125 and anti-biotin epitopes was used with PEGylated liposomes coated with biotin to deliver the cytotoxic radionuclide 90Y to tumor sites. This approach was used to overcome some of the major obstacles associated with conventional strategies, in particular, to increase the amount of radioactivity delivered to the tumor site compared with conventional monoclonal antibody (MAb) radionuclide delivery. Sequential intraperitoneal administration of the targeting and therapeutic moieties provides the basis for enhanced therapeutic ratio, according to our strategy. We report here the results of an in vivo therapy using our RIT approach with the Balb/c nude mouse model xenografted with the NIH:OVCAR-3 (CA 125+) human ovarian cancer cell line. An ongoing tumor growth delay/control study in Balb/c mice xenografted intraperitoneally with the NIH:OVCAR-3 cell line indicates a significant delay in onset of tumor and ascites development in treated vs. control populations.