IDO inhibitors for combinatorial cancer therapy

用于组合癌症治疗的 IDO 抑制剂

基本信息

批准号：
8476989
负责人：
GEORGE C PRENDERGAST
金额：
$ 22.95万
依托单位：
LANKENAU INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8476989
关键词：
Address Animals Award Biochemical Biological Assay Cancer Patient Caring Cells Characteristics Clinic Clinical Trials Collaborations Computer Simulation Cytotoxic Chemotherapy Development Disease Disseminated Malignant Neoplasm Enzymes Evolution Generations Genetic Goals Government Grant Immune Immune system Immunologic Surveillance In Vitro Inflammatory Intellectual Property Lead Malignant - descriptor Malignant Neoplasms Mediating Methods Modeling Patients Pharmaceutical Preparations Pharmacology Phase Radiation therapy Recruitment Activity Research Personnel Series T-Lymphocyte Translations Tryptophan 2,3 Dioxygenase Tumor Escape Work base cancer immunotherapy cancer therapy carcinogenesis chemotherapy clinical application combinatorial cost improved in vivo inhibitor/antagonist neoplastic cell pre-clinical programs research clinical testing research study response small molecule standard of care trait tumor tumor growth tumor microenvironment

项目摘要

DESCRIPTION (provided by applicant): During their development tumors acquire the capability to escape immune control. Immune escape is a fundamental trait of cancer but until recently there was little understanding of how it develops. IDO is an enzyme that we and others have found to drive immune escape in tumors, where IDO is often inappropriately switched on. Our progress during the original 3-year grant award established genetic and pharmacological proofs that IDO is essential to support inflammatory carcinogenesis and malignant progression. We now seek to pursue a drug-like series that offers second generation improvements to a lead compound that we brought forward to clinical testing (currently in Phase I/IB trials) as a result of a successful FDA IND application generated in collaboration with academic and government investigators and a biopharma company that outlicensed our IDO intellectual property. Continued pursuit of the work, which our group has pioneered as a radically new cancer immunochemotherapy, will generate clinically applicable IDO inhibitors that stimulate the immune system to attack tumors in an animal in a manner that greatly leverages concomitant standard-of-care chemotherapy or radiotherapy. These second generation compounds will address deficiencies in the present experimental lead compound, which may be appropriate for proof-of-concept experiments in clinic but perhaps less suited as a drug for more general mechanism-based clinical applications. The intellectual thrust of this project will continue address the top priority of the field to improve the treatment of metastatic cancers, where recruiting the patient's own immune system by IDO inhibition in combination with standards of care could offer a low cost, broadly applicable, and highly effective method for disease treatment.

描述（由申请人提供）：在肿瘤的发育过程中，肿瘤获得了逃避免疫控制的能力。免疫逃逸是癌症的一个基本特征，但直到最近，人们对其如何发展还知之甚少。我们和其他人发现 IDO 是一种在肿瘤中驱动免疫逃逸的酶，而 IDO 经常在肿瘤中被不适当地开启。我们在最初的 3 年资助期间取得的进展证明了 IDO 对于支持炎症癌变和恶性进展至关重要。我们现在寻求开发一个类药物系列，对先导化合物进行第二代改进，由于与学术界和学术界合作成功提交了 FDA IND 申请，我们将其推进临床测试（目前处于 I/IB 期试验）。政府调查人员和一家生物制药公司授予了我们 IDO 知识产权的许可。我们小组率先将这项工作作为一种全新的癌症免疫化疗，继续开展这项工作将产生临床适用的 IDO 抑制剂，刺激免疫系统以极大地利用伴随的标准护理化疗或放疗的方式攻击动物的肿瘤。这些第二代化合物将解决目前实验先导化合物的缺陷，其可能适合临床概念验证实验，但可能不太适合作为更一般的基于机制的临床应用的药物。该项目的智力主旨将继续解决该领域的首要任务，即改善转移性癌症的治疗，其中通过 IDO 抑制与护理标准相结合来招募患者自身的免疫系统可以提供低成本、广泛适用和高度的治疗效果。治疗疾病的有效方法。