Immune-based brain cancer diagnostic for rapid, accurate disease classification

描述(由申请人提供)：准确、早期的疾病诊断和监测是有效预防、治疗和缓解疾病的关键方面。目前可用的大多数诊断方法还不够简单或灵敏，不足以显著影响患者对治疗或生存结果的反应。这种未得到满足的需求因脑癌等疾病而突显出来，这些疾病往往在早期阶段保持无症状，然后迅速增长--产生快速、致命的结果。我们发明了免疫标记(IS)作为一种新的疾病诊断方法，以解决这些问题。IS是基于对血清的查询。使用抗体作为疾病的生物标志物利用了稳定和容易获得的分子以及免疫系统的多样性、监测和生物放大的便利特性。哺乳动物免疫系统的复杂性令人震惊，信息内容也是如此。成本的降低，免除了手术，成像，以及这种快速检测的简单性，为频繁、准确地监测缓解期和新疗法试验中的患者铺平了道路。这里提出的创新计划将成为一种快速、准确的诊断工具，并展示其对脑癌的有效性。 在第一阶段，我们将验证HealthTell平台的能力，以识别能够准确诊断胶质瘤与其他癌症的多肽模拟表位(从330,000个随机序列库中选择)，并根据它们的病理类型和级别以及分子亚型对它们进行分类。这些将在第二阶段进行严格的探索和扩展，以包括对额外重要群体的分析：较低级别的原发胶质瘤和继发性脑癌，如转移性肺癌和乳腺癌。将健康志愿者的血清纳入与患者地理位置匹配的地点，并进行额外的盲群研究，将为建立高水平的绩效指标提供数据。在这项计划的期限内，肽签名将促进缓解期和治疗监测，使胶质瘤能够更有效地管理，包括更好地调节化疗和放射，以及对新的靶向治疗进行更快、更准确的评估。我们打算与位于圣约瑟夫医院医学中心/巴罗斯神经研究所(BNI)园区的CAP/CLIA认证的DNA诊断实验室合作，进行与传统诊断相关的商业化和验证。再加上BNI看的脑瘤患者比美国其他任何地方都多，我们为迅速将这一诊断产品投入临床应用做好了充分的准备。除了这项计划外，在这项计划中识别和验证的多肽生物标记物将在一个单一的、通用的健康芯片上作为新的脑癌的早期监视犬。这与HealthTell的商业计划相一致，该计划将一种简单、廉价的微芯片商业化，以监测无症状的人的早期疾病发展。对健康人的持续监测将有助于及早发现脑癌征兆等干扰因素。

DESCRIPTION (provided by applicant): Accurate, early disease diagnosis and monitoring are critical aspects to effective prevention, treatment, and remission of disease. Most diagnostic methods available today are not simple or sensitive enough to significantly impact patients' response to treatment or survival outcome. This unmet need is highlighted by diseases, such as brain cancers, that often remain asymptomatic at early stages and then grow aggressively- with fast, fatal outcomes. We have invented immunosignatures (IS) as a new approach to disease diagnoses that addresses these problems. IS is based on querying blood-serum. Using antibodies as biomarkers of disease takes advantage of a stable and easily accessible molecule and the immune system's convenient properties of diversity, surveillance, and biological amplification. The complexity of a mammalian immune system is staggering and therefore so is the information content. The reductions in cost, elimination of surgery, imaging, and the simplicity of this rapid assay pave the way to frequent, accurate monitoring of individuals in remission and those in trials with new therapies. The innovative program presented here will build IS into a rapid, accurate diagnostic tool and demonstrate its effectiveness for brain cancer. In phase I we will validate the power of HealthTell's platform to identify peptide mimotopes (selected from a library of 330,000 random sequences) that accurately diagnose gliomas from other cancers, and classify them relative their pathological types and grades, and molecular subtypes. These will be rigorously explored and expanded in phase II to include analyses of additionally important groups: the lower grade primary gliomas and secondary brain cancers such as metastatic lung and breast cancers. Inclusion of sera from healthy volunteers in geographically matched sites relative to patients and additional blinded cohorts studies will provide data for high level performance metrics to be established. Within the term of this program, the peptide signatures will facilitate remission-stage and treatment monitoring, enabling more effective management of gliomas including better modulation of chemotherapy and radiation, and faster, more accurate evaluations of new targeted therapies. We intend to partner with the CAP/CLIA certified DNA Diagnostics Laboratory situated on the St. Joseph's Hospital Medical Center/Barrows Neurological Institute (BNI) campus for commercialization and validation relative to conventional diagnostics. Combined with the fact that BNI sees more brain tumor patients than any other place in the US, we are strongly positioned for moving this diagnostic product quickly into clinical use. Beyond this program, the peptide biomarkers identified and validated in this program will serve as early stage watch-dogs for new brain cancers on a single, universal health chip. This aligns with HealthTell's business plan of commercializing a simple, inexpensive microchip to monitor asymptomatic people for early development of disease. Continuous monitoring of healthy people would permit perturbations, such as brain cancer signatures, to be detected early.