用于癌症治疗的抗体-药物缀合物-猫眼课题宝

用于癌症治疗的抗体-药物缀合物

批准号：

3492997

负责人：

RAVI V CHARI

金额：

$5.0万

依托单位：

IMMUNOGEN, INC.

依托单位国家：

美国

项目类别：

财政年份：

1992

资助国家：

美国

项目状态：

已结题

起止时间：

1992-07-01 至 1992-12-31

来源：

https://reporter.nih.gov/project-details/3492997

关键词：

chemical synthesis cytotoxicity disulfide bond drug adverse effect drug design /synthesis /production esterification immunoconjugates laboratory mouse monoclonal antibody neoplasm /cancer chemotherapy neoplasm /cancer pharmacology nonhuman therapy evaluation thiols

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英文摘要

The aim of this project is to produce monoclonal antibody-drug conjugates with therapeutic potency for the selective destruction of human cancer cells. It is stated that antibody-drug conjugates prepared by current approaches do not achieve high levels of free drug inside targeted cells. It is proposed to replace the current moderately cytotoxic anti-cancer drugs with maytansinoids which are 100 to 1000 fold more cytotoxic. The maytansinoids will be linked via disulfide bonds, which are stable in circulation, but cleaved intracellularly. The maytansinoids will be synthetically modified to incorporate disulfide or thiol groups. The most cytotoxic of these drugs will be conjugated to monoclonal antibodies by disulfide bonds and assessed for in vitro cytotoxicity to cancer cells. In vivo pharmacokinetic properties will be evaluated in mice.

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