Decoy Peptides: Development of a Novel Therapeutic for Metastatic Cancer

诱饵肽：转移性癌症新疗法的开发

基本信息

批准号：
8838987
负责人：
Todd D Camenisch
金额：
$ 11.96万
依托单位：
ARIZONA CANCER THERAPEUTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-23 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8838987
关键词：
American Animals Apoptosis Arizona Automobile Driving Binding Biological Assay Biotechnology Breast Cancer Cell Breast Cancer Treatment Breast Carcinoma Cancer Center Cancer Patient Cancer cell line Cells Cessation of life Clinical Trials Combined Modality Therapy Development Disseminated Malignant Neoplasm Docking Dose Drug Kinetics Epidermal Growth Factor Receptor Event Experimental Designs FDA approved Goals Growth Health Human Immune response Immunity Immunotherapy Investigational Drugs Laboratory Research Legal patent Life Lung Neoplasms MDA MB 231 Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of ovary Malignant neoplasm of pancreas Metabolism Metastatic Neoplasm to the Breast Methods Mission Molecular Mouse Mammary Tumor Virus Mucin-1 Staining Method Mus Neoplasm Metastasis Oncogene Proteins Oncogenic Patients Peptides Pharmaceutical Preparations Pharmacology Pharmacology and Toxicology Phase Phase II Clinical Trials Property Protein Analysis Proteins Publications Publishing Reporting Research Research Contracts Research Project Grants Therapeutic Toxic effect Toxicology Transgenic Mice Tumor Expansion United States National Institutes of Health Universities Vaccines Work absorption antitumor drug base burden of illness cancer cell cell growth chemotherapy combinatorial design disability drug candidate effective therapy extracellular good laboratory practice improved malignant breast neoplasm mouse model neoplastic cell novel novel strategies novel therapeutics ovarian neoplasm pancreatic neoplasm patient population pre-clinical pre-clinical research preclinical study protein profiling protein protein interaction public health relevance therapeutic protein therapeutic target tumor tumor growth tumor progression uptake

项目摘要

DESCRIPTION (provided by applicant): Arizona Cancer Therapeutics LLC (ACT) proposes a two-year, preclinical research project in cooperation with the University of Arizona Cancer Center to develop the novel anti-tumor therapeutic, Protein transduction domain-MUC1 Inhibitory Peptide (PMIP). PMIP is an intracellular MUC1 peptide that acts as a decoy to block the MUC1- oncoprotein interactions that drive breast cancer growth and metastasis. Utilizing a protein transduction domain to allow for transmembrane cellular uptake, PMIP can freely enter the cell and interact with intracellular target proteins. Laboratory research at the University of Arizona over the past nine years has examined the ability of MUC1 and an oncogenic partner, epidermal growth factor receptor (EGFR), to synergistically drive breast cancer progression. To block these tumor-specific, intracellular interactions, the first-in-class peptide-based cancer therapeutic, PMIP, was developed. Studies in tumor-bearing mouse models demonstrate that PMIP blocks tumor growth and metastasis and is nontoxic and tumor specific, making it an excellent anti-tumor drug candidate to carry forward through preclinical studies and clinical trials. Over 40,000 Americans die annually from metastatic breast cancer and, in greater than 90 percent of human breast carcinomas and metastases, MUC1 is over-expressed. This project represents critical steps in preclinical studies in drug dosing, absorption, distribution, metabolism and toxicity. The project will also investigate the benefits of PMIP when used in combination with FDA-approved chemotherapies for breast cancer. PMIP represents a unique approach to targeting MUC1 activities in cancer - other clinical trials targeting MUC1 have been designed to elicit anti-MUC1 immunity, and have been largely ineffective. Unlike these approaches, PMIP does not rely on activation of the immune response, but instead directly blocks tumor-promoting intracellular interactions. If successful, PMIP can substantially enhance the effective treatment options for metastatic breast cancer patients. This project aligns to NIH's mission to enhance health, lengthen life, and reduce the burdens of illness and disability by researching a new and unique anti-tumor drug to treat, effectively and with low or no toxicity, metastatic breast cancer.

描述（由申请人提供）：Arizona Cancer Therapeutics LLC (ACT) 提出与亚利桑那大学癌症中心合作开展一项为期两年的临床前研究项目，开发新型抗肿瘤治疗药物——蛋白质转导结构域 - MUC1 抑制肽 (PMIP) ）。 PMIP 是一种细胞内 MUC1 肽，可作为诱饵来阻断促进乳腺癌生长和转移的 MUC1-癌蛋白相互作用。利用蛋白质转导结构域允许跨膜细胞摄取，PMIP 可以自由进入细胞并与细胞内靶蛋白相互作用。亚利桑那大学过去九年的实验室研究检验了 MUC1 和致癌伙伴表皮生长因子受体 (EGFR) 协同驱动乳腺癌进展的能力。为了阻断这些肿瘤特异性的细胞内相互作用，开发了一流的基于肽的癌症治疗剂 PMIP。对荷瘤小鼠模型的研究表明，PMIP可阻断肿瘤生长和转移，且无毒且具有肿瘤特异性，使其成为可通过临床前研究和临床试验进行推广的优秀抗肿瘤候选药物。每年有超过 40,000 名美国人死于转移性乳腺癌，并且在超过 90% 的人类乳腺癌和转移瘤中，MUC1 过度表达。该项目代表了药物剂量、吸收、分布、代谢和毒性方面临床前研究的关键步骤。该项目还将研究 PMIP 与 FDA 批准的乳腺癌化疗药物联合使用时的益处。 PMIP 代表了一种针对癌症中 MUC1 活性的独特方法 - 其他针对 MUC1 的临床试验旨在引发抗 MUC1 免疫力，但基本上无效。与这些方法不同的是，PMIP 不依赖于免疫反应的激活，而是直接阻断促进肿瘤的细胞内相互作用。如果成功，PMIP 可以大大增强转移性乳腺癌患者的有效治疗选择。该项目符合 NIH 的使命是通过研究一种新的、独特的抗肿瘤药物来有效地、低毒性或无毒性地治疗转移性乳腺癌，从而增强健康、延长寿命、减轻疾病和残疾负担。