Diagnosis, Prognosis and Treatment of hRgr associated Hematopoietic Malignancies

hRgr 相关造血系统恶性肿瘤的诊断、预后和治疗

• 批准号: 8314901
• 负责人: Peter Leonardi
• 金额: $ 19.92万
• 依托单位: OMNICYTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-26 至 2016-03-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8314901
• 关键词: Acute Lymphocytic Leukemia; Adverse effects; Animal Model; Antibodies; Applications Grants; Biological Assay; Biotechnology; Cell Line; Cells; Child; Clinical; Clinical Trials; Collaborations; Companions; Complement; Data; Development; Diagnosis; Diagnostic; Doctor of Philosophy; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Fluorochrome; Foundations; Goals; Grant; Hematopoietic Neoplasms; Immunohistochemistry; Immunophenotyping; In Vitro; Incentives; Individual; Institution; Intellectual Property; Investments; Legal patent; Licensing; Malignant Neoplasms; Marketing; Medical center; Minority; Mission; Molecular; Monoclonal Antibodies; Mutate; Mutation; New York City; Oncogene Proteins; Oncogenes; Oncogenic; Orphan Drugs; Outcome; Paraffin Embedding; Patient Selection; Patients; Pharmaceutical Preparations; Phase; Positioning Attribute; Prevalence; Production; Proteins; Recurrence; Regimen; Relapse; Remission Induction; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Screening procedure; Selection for Treatments; Specificity; Study Subject; Subgroup; T-Cell Lymphoma; T-Lymphocyte; T-Lymphocyte Subsets; Technology; Testing; Therapeutic; Therapeutic Uses; base; cancer therapy; improved; interest; leukemia/lymphoma; mutant; novel; outcome forecast; patient population; prognostic; programs; response; small molecule; success; therapeutic target

DESCRIPTION (provided by applicant): OmniCyte is dedicated to the development of novel targeted treatments for T-Cell malignancies. The company will pursue the development of a commercial diagnostic specifically targeted at a subgroup of T- cell malignancies, including Acute Lymphoblastic Leukemia (ALL). Because T-cell lymphomas and leukemias generally make up the minority of each type of lymphoma and leukemia, and therapeutics are traditionally developed to treat the majority, it is not surprising that T-cell malignancies often do not respond as well to therapeutics. Thus they require more intense treatment that results in worse side effects, and when there is recurrence it is most often deadly. Therefore, not only is there a need for more emphasis on therapeutics for T-Cell cancers, there is a need to improve the arsenal of diagnostics to complement that emphasis. hRgr is a novel oncogene that has been found to be mutated and over-expressed in numerous T- cell cancers. It has also been shown to be transforming in vitro and animal models. When inactivated, hRgr has been shown to reverse transformation in T-cell malignancies. OmniCyte in collaboration with NYU Medical Center, plans to develop a diagnostic, for prognosis, to determine treatment options, and to complement the development of a small molecule therapeutics targeted at hRgr. For the diagnostic we will attempt to develop both a monoclonal antibody that can be used in Flow Cytometry (to detect the presence of the mutant protein in permeablized cells) as well as a monoclonal antibody to be used in immunohistochemistry. Both assays are currently being used for diagnosis and prognosis of hemopoetic malignancies, and the availability of both assays will make testing for the expressed activated oncogene possible at institutions of various sizes and capabilities. For our companion diagnostic, it may be possible to use the RT-PCR assay already employed in our lab. While we have begun to develop a therapeutic to treat these malignancies, the diagnostic assays are of paramount importance to stratify the study subjects of a clinical trial. Additionally the diagnostics will be necessary to target the minority subset of patients that may benefit from a therapeutic. Possibly more importantly, the assay may offer prognosis information and may direct the therapeutics used in treatment of hemopoetic malignancies, particularly to avoid relapse and/or following relapse. It is our great desire to develop a clinical diagnostic to aid in the targeted treatment of cancer. To effectively realize the commercial potential of our efforts we hope to enjoy incentives such as Orphan Drug Status, which provides grant opportunities, FDA approval support, and 7 year market exclusivity. Additionally, the company has already begun to leverage foundation support and that of altruistically interested individuals. Finally, we are positioning the program and its intellectual property so that it will be of interest to pharma companies and other institutional investors when we reach critical clinical milestones. PUBLIC HEALTH RELEVANCE: T-cell malignancies make up the minority of each type of lymphoma and leukemia, and the treatments are traditionally developed to treat the majority, therefore it is not surprising that T-cell malignancies often do not respond as well to the treatments. OmniCyte is pursuing the commercial development of a diagnostic to identify the subset of T-cell patients who express the hRgr mutation. By examining retrospective patient data, we will also attempt to determine the prognosis of these patients and identify the therapeutic options with the greatest chance of success for this underserved subgroup. Finally, we will develop a companion diagnostic for a small molecule therapeutics that we are currently developing to specifically target this subgroup of patients. A companion diagnostic is necessary for a therapeutic that specifically targets the oncogene product to be useful.

描述（由申请人提供）：全冻致力于开发针对T细胞恶性肿瘤的新型靶向治疗方法。该公司将寻求专门针对T细胞恶性肿瘤亚组的商业诊断，包括急性淋巴细胞性白血病（ALL）。由于T细胞淋巴瘤和白血病通常构成每种类型的淋巴瘤和白血病的少数，并且传统上开发了治疗剂来治疗大多数人，因此T细胞恶性肿瘤通常不会反应不足为奇 以及治疗学。因此，它们需要更激烈的治疗，从而导致副作用更严重，并且当复发时，它通常是致命的。因此，不仅需要更多地强调T细胞癌的治疗剂，而且还需要改善诊断的武器库来补充强调的重点。 HRGR是一种新型的癌基因，已发现在许多T细胞癌中被突变和过表达。它也已显示在体​​外和动物模型中转化。当灭活时，HRGR已被证明会在T细胞恶性肿瘤中逆转转化。 Omnicyte与纽约大学医学中心合作，计划开发一种诊断，预后，确定治疗方案，并补充针对HRGR的小分子疗法的开发。对于诊断，我们将尝试开发一种可以用于流式细胞仪（检测渗透性细胞中突变蛋白的存在）的单克隆抗体以及用于免疫组织化学中的单克隆抗体。目前，这两种测定法都用于诊断和预后，对血液恶性肿瘤进行了预后，两种测定的可用性将使在各种规模和能力的机构中对表达的激活癌基进行测试。对于我们的伴侣诊断，可能可以使用我们实验室中已经使用的RT-PCR测定法。尽管我们开始开发一种治疗这些恶性肿瘤的治疗方法，但诊断测定对于对临床试验的研究对象进行分层至关重要。此外，对于可能受益于治疗性的患者的少数群体子集将是必要的。更重要的是，该测定可能提供预后信息，并可能指导用于治疗血液疾病恶性肿瘤的治疗剂，特别是为了避免复发和/或复发后。我们渴望开发临床诊断以帮助进来的渴望 癌症的靶向治疗。为了有效地实现我们努力的商业潜力，我们 希望享受激励措施，例如孤儿毒品状况，提供赠款机会，FDA批准支持和7年市场的独家。此外，该公司已经开始利用基金会的支持和利他感兴趣的人的支持。最后，我们将该计划及其知识产权定位，以便在达到关键的临床里程碑时，制药公司和其他机构投资者都会感兴趣。 公共卫生相关性：T细胞恶性肿瘤构成了每种类型的淋巴瘤和白血病的少数，并且传统上开发了治疗方法来治疗大多数人，因此，T细胞恶性肿瘤通常对治疗方法的反应也不足为奇。 Omnicyte正在追求诊断的商业开发，以识别表达HRGR突变的T细胞患者的子集。通过检查回顾性患者数据，我们还将尝试确定这些患者的预后，并确定该服务不足的亚组成功机会的治疗选择。最后，我们将开发用于一种小分子疗法的伴侣诊断，目前我们正在开发该诊断，以专门针对该亚组患者。伴侣诊断对于专门针对癌基产品有用的治疗性是必要的。