IDO inhibitors for combinatorial cancer therapy

描述（由申请人提供）：肿瘤在发育过程中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，人们对它是如何发展的知之甚少。IDO是一种酶，我们和其他人已经发现它可以在肿瘤中驱动免疫逃逸，在肿瘤中IDO经常被不适当地打开。在最初的3年资助期间，我们的进展建立了遗传和药理学证据，证明IDO对支持炎症性癌变和恶性进展至关重要。我们现在寻求一个类似药物的系列，提供第二代改进的先导化合物，我们提出了临床试验（目前在I/IB期试验），作为一个成功的FDA IND申请产生与学术和政府研究人员和生物制药公司合作，授权我们的IDO知识产权。我们的团队开创了一种全新的癌症免疫化疗，继续追求这项工作，将产生临床适用的IDO抑制剂，刺激免疫系统以一种极大地利用伴随的标准护理化疗或放疗的方式攻击动物体内的肿瘤。这些第二代化合物将解决目前实验先导化合物的不足，该先导化合物可能适用于临床的概念验证实验，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。该项目的智力动力将继续解决该领域的首要任务，以改善转移性癌症的治疗，其中通过IDO抑制招募患者自身免疫系统并结合标准护理可以提供低成本，广泛适用且高效的疾病治疗方法。

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.