HOMING PEPTIDES FOR THE VASCULATURE IN PROSTATE

前列腺血管的归巢肽

• 批准号: 7311229
• 负责人: ERKKI RUOSLAHTI
• 金额: $ 29.13万
• 依托单位: SIDNEY KIMMEL CANCER CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7311229
• 关键词: antineoplastics; antireceptor antibody; cell surface receptors; disease /disorder model; drug design /synthesis /production; genetically modified animals; human tissue; laboratory mouse; molecular oncology; neoplasm /cancer blood supply; neoplasm /cancer chemotherapy; neoplastic growth; nonhuman therapy evaluation; peptide library; peptides; prostate neoplasms; therapy design /development; vascular endothelium

This component will apply peptide library-based vascular targeting developed in the project leader's laboratory to profile molecular alterations in vasculature during prostate tumorigenesis. New peptides for both the blood vessel and lymphatic vasculature of prostate cancer will be isolated and their utility as tools for therapeutic targeting of prostate diseases will be explored. The design of the screening will favor peptides that generally recognize prostate cancer vasculature, rather than being selective for an individual prostate cancer model. The specificity of these peptides will be ascertained by testing peptide binding to normal and cancerous tissues from mice and from human patients. The target molecules ('receptors") for the most promising peptides will be identified and antibodies will be prepared against the receptors. The peptides identified and characterized as described above and antibodies prepared against their receptors will be tested for their effects on prostate cancer vasculature and tumor growth, and their ability to deliver peptide-drug or antibody-drug conjugates to pre-malignant prostate lesions and prostate cancers. Promising compounds emerging from these experiments will be tested in pre-clinical prostate cancer models for prevention and treatment of prostate cancer. New information on tissue- and tumor-specific vasculature specialization will be gained from this study. New therapies for preventing the development of prostate cancer and for treating established prostate cancer may emerge.

该成分将采用基于肽库的基于肽库的血管靶向在项目领导者的实验室中开发的，以介绍前列腺肿瘤发生过程中血管的分子改变。将分离出血管和淋巴管脉管系统的新肽，并将探索它们作为治疗性靶向前列腺疾病的工具。筛查的设计将有利于通常识别前列腺癌脉管系统的肽，而不是对单个前列腺癌模型的选择性。这些肽的特异性将通过测试与小鼠和人类患者的正常和癌组织结合的肽结合来确定。将鉴定出最有前途的肽的靶分子（“受体”），并准备针对受体的抗体。肽。 如上所述鉴定和表征，针对其受体制备的抗体对它们对前列腺癌脉管系统和肿瘤生长的影响以及它们输送肽 - 药物或抗体 - 毒剂结合物的能力进行测试。这些实验中出现的有希望的化合物将在预防和治疗前列腺癌的临床前前列腺癌模型中进行测试。这项研究将获得有关组织和肿瘤特异性脉特专业化的新信息。防止前列腺癌发展和治疗的新疗法 建立的前列腺癌可能会出现。