IMPROVING TUMOR RADIOIMMUNOTHERAPY BY PNA PRETARGETING

描述：预重定向方法被认为可以克服 与传统放射免疫治疗(RAIT)相关的问题 放射性核素附着在抗体上。最具针对性的研究 使用亲和素/生物素识别系统。即使临床试验 都提供了令人鼓舞的结果，(链霉亲和素)已被发现 高度免疫原性和内源性生物素已被证明干扰 瞄准目标。用低聚物替代生物素和(链)亲和素 对于预先定位的本地化有可能消除这些 有问题。低聚物与其结合具有高亲和力和特异性 补充，不存在内源性低聚物问题。低聚物 磷酸二酯和硫代磷酸脱氧核糖核酸被认为是 预先靶向，由于体内快速降解而被发现不适合 前者的大趋势和后者的大趋势使其符合常态 纸巾。提出了一种新型的多肽核酸(PNAS) 用于PNA将在哪里的预瞄准方法的识别系统 与抗体结合。清除未结合循环抗体后 有了抗独特型抗体，放射性核素将通过 免费赠送的一股PNA。最终，一种预瞄准系统，包括 设想了单独的CDR-grated靶向和清除抗体。 建议的商业应用：不可用

DESCRIPTION: Pretargeting approaches have been considered to overcome problems associated with conventional radioimmunotherapy (RAIT) where the radionuclide is attached to the antibody. Most pretargeting studies employ an avidin/biotin recognition system. Even though clinical trials are providing encouraging results, (strept) avidin has been found to be highly immunogenic and endogenous biotin has been shown to interfere with targeting. The use of oligomers in place of biotin and (strept) avidin for pretargeting localization has the potential to eliminate these problems. Oligomers bind with high affinity and specificity to their complement and there is no endogenous oligomer problem. Oligomeric phophodiester and phosphorothioate DNAs have been considered for pretargeting, and found to be unsuitable due to rapid in vivo degradation of the former and the great tendency of the latter to bind to normal tissues. Peptide nucleic acids (PNAs) are proposed here as the novel recognition system for a pretargeting approach where PNA will be conjugated to an antibody. After clearing unbound circulating antibody with an anti-idiotypic antibody, radionuclide will be delivered via the complimentary strand of PNA. Ultimately, a pretargeting system comprising solely cdr-grated targeting and clearance antibodies is envisaged. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE