论文部分内容阅读
目的:研究125I标记的抗p185抗体(鼠mAbA21、人鼠嵌合抗体A21scFv-Fc及单链抗体A21scFv)在体外的细胞代谢和在体内的生物学分布,为其在诊断和治疗高表达p185肿瘤的临床应用提供依据。方法:通过FACS检测抗体是否与高表达膜表面抗原p185的SKOV3特异结合。采用氯胺T法进行碘标记抗体,用细胞放射免疫分析实验,检测抗体在SKOV3细胞中的代谢。建立荷SKOV3裸鼠模型,以观察抗体的体内生物学分布。结果:体外细胞代谢实验表明,抗体在与细胞膜表面结合后,进而被内吞入细胞,在细胞内降解和脱碘,最后被分泌出细胞外。体内药物代谢实验表明,抗体在动物体内肿瘤部位出现选择性放射性浓聚,而无关抗体未出现放射性浓聚,呈全身分布。结论:mAbA21,A21scFv-Fc和A21scFv对于高表达p185的卵巢癌在体内和体外都具有亲和力,可望用作高表达p185肿瘤的诊断和治疗。
AIM: To study the cellular metabolism and in vivo biological distribution of 125I-labeled anti-p185 antibody (murine mAbA21, human mouse chimeric antibody A21scFv-Fc and scFv A21scFv) in vitro for its clinical significance in the diagnosis and treatment of high expression of p185 tumor Provide the basis for clinical application. Methods: Whether FACS specifically binds to SKOV3 highly expressing membrane surface antigen p185 is detected by FACS. Chloramine T method was used to iodine-labeled antibody, cell radioimmunoassay experiments to detect the antibody in SKOV3 cell metabolism. The SKOV3 nude mice model was established to observe the in vivo biological distribution of the antibodies. RESULTS: In vitro cell metabolism experiments showed that the antibody was endocytosed into the cell after it bound to the cell membrane surface, degraded and deiodinated in the cell, and finally secreted out of the cell. In vivo drug metabolism experiments show that the antibody in the body of animals showed selective radioactive accumulation of the tumor, while the non-related antibodies did not appear radioactive enrichment, showed systemic distribution. Conclusion: mAbA21, A21scFv-Fc and A21scFv have affinity both in vivo and in vitro for overexpressing ovarian cancer p185 and are expected to be used as a diagnosis and treatment for overexpressing p185 tumors.