IMPROVING TUMOR RADIOIMMUNOTHERAPY BY PNA PRETARGETING

通过 PNA 预靶向改善肿瘤放射免疫治疗

• 批准号: 2645330
• 负责人: HABIBE KARACAY
• 金额: $ 10万
• 依托单位: IMMUNOMEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-22 至 1999-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2645330
• 关键词: bioengineering /biomedical engineering; drug design /synthesis /production; immunoconjugates; method development; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide therapy; nucleic acids; peptides; radiopharmacology; technetium

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

描述：预靶向方法被认为可以克服 与常规放射免疫疗法（赖特）相关的问题， 放射性核素附着于抗体。 大多数预靶向研究 使用抗生物素蛋白/生物素识别系统。 尽管临床试验 提供了令人鼓舞的结果，（链球菌）抗生物素蛋白已被发现是 已显示高度免疫原性和内源性生物素干扰 面向. 使用寡聚物代替生物素和（链霉菌）抗生物素蛋白 对于预定位定位有可能消除这些 问题寡聚体以高亲和力和特异性结合到它们的 补体，并且没有内源性寡聚体问题。 低聚 磷酸二酯和硫代磷酸DNA已经被考虑用于 预靶向，并发现由于体内快速降解而不适用 第一个是前者，第二个是后者， 组织中 肽核酸（PNAs）在这里提出的新的 识别系统的预靶向方法，其中PNA将 与抗体缀合。 清除未结合循环抗体后 使用抗独特型抗体，放射性核素将通过 PNA的互补链。 最终，一种预靶向系统，包括： 设想了仅CDR-分级的靶向和清除抗体。 拟议商业应用：不可用