Long-Acting VEGF Binding Proteins for Treating Cancer

用于治疗癌症的长效 VEGF 结合蛋白

• 批准号: 6784974
• 负责人: MARY S. ROSENDAHL
• 金额: $ 10万
• 依托单位: BOLDER BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6784974
• 关键词: angiogenesis; antineoplastics; binding proteins; biotechnology; biotherapeutic agent; cell line; cysteine; drug design /synthesis /production; drug screening /evaluation; gene expression; gene mutation; growth factor receptors; laboratory rat; molecular cloning; neoplasm /cancer chemotherapy; pharmacokinetics; polyethylene glycols; protein engineering; protein purification; protein structure function; protein tyrosine kinase; receptor binding; recombinant proteins; tissue /cell culture; vascular endothelial growth factors

DESCRIPTION (provided by applicant): Vascular endothelial growth factor (VEGF) has been identified as a key mediator of tumor angiogenesis and has emerged as the single most commonly upregulated angiogenic factor in both grafted and naturally occurring tumors. VEGF exerts its biological activity by binding to its tyrosine kinase receptors, VEGF-R1 (Flt-1) and VEGF-R2 (Flk-1/KDR). Preclinical studies have examined the biological activities of different types of VEGF antagonists, including anti-VEGF neutralizing antibodies, soluble versions of the receptor molecules, and inhibitors of VEGF-R2 tyrosine kinase. In each case, significant inhibition of tumor growth and reduced vasculature was observed. We propose to prepare and evaluate long acting versions of one of these antagonists, specifically VEG-R1 receptor (Fit-l). During Phase I we will identify sites in the soluble portion of Flt-1 (sFlt-1) that can be modified with an inert polymer without significantly affecting the protein's in vitro bioactivity. During Phase II, we will manufacture sufficient quantities of the modified sFlt-1 proteins for testing in animal models of cancer. Based on our previous work, these modified sFlt-1 proteins should be superior to the present preparations of recombinant soluble Flt-1. In particular we expect to see improved stability, higher potency, greater solubility, longer circulating half-lives, less frequent dosing and reduced antigenicity. These improved biological and physical characteristics should expedite pre-clinical and clinical evaluation of sFlt-1 as an anti-angiogenesis agent.

描述（由申请人提供）：