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: 8745193
• 负责人: Peter Leonardi
• 金额: $ 17.34万
• 依托单位: OMNICYTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-15 至 2016-03-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8745193
• 关键词: Acute Lymphocytic Leukemia; Adverse effects; Animal Model; Antibodies; Applications Grants; Back; Biological; Biological Assay; Biotechnology; Cell Line; Cells; Child; Clinical; Clinical Trials; Collaborations; Companions; Complement; Data; Development; Diagnosis; Diagnostic; Doctor of Philosophy; Enzyme-Linked Immunosorbent Assay; Equipment; Flow Cytometry; Fluorochrome; Foundations; Goals; Grant; Hematopoietic Neoplasms; Hurricane; 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; Natural Disasters; 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; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Selection for Treatments; Small Business Technology Transfer Research; Specificity; Study Subject; Subgroup; T-Cell Lymphoma; T-Lymphocyte; T-Lymphocyte Subsets; Technology; Testing; Therapeutic; Therapeutic Uses; Time; base; cancer therapy; improved; interest; leukemia/lymphoma; mutant; novel; outcome forecast; patient population; prognostic; programs; response; screening; small molecule; success; therapeutic target

OmniCyte, and its collaborative STTR project with NYU Medical Center, were dramatically impacted by the natural disaster, hurricane Sandy. Sandy hit only one month into our project and it is only in the last two weeks have we been able to get back into our lab at NYU. We have endured 11 months of being dislodged. During that time we have lost most biological resources as well as access to key equipment. Despite challenges form Sandy, 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 Tcell 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 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 therapeutic 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.

Omnicyte及其与纽约大学医疗中心的协作STTR项目受到了极大的影响 自然灾害，桑迪飓风。桑迪只打入我们的项目一个月，只有最后一个 两个星期我们能够回到纽约大学的实验室。我们已经忍受了11个月的时间 脱落。在此期间，我们失去了大多数生物资源以及使用关键设备。 尽管桑迪构成了挑战，但Omnicyte仍致力于发展新颖的目标治疗 用于T细胞恶性肿瘤。该公司将追求商业诊断的开发 专门针对T细胞恶性肿瘤的亚组，包括急性淋巴细胞白血病（ALL）。 因为T细胞淋巴瘤和白血病通常构成每种类型的淋巴瘤的少数 传统上为治疗大多数人而开发了白血病和治疗剂，TCELL毫不奇怪 恶性肿瘤通常对治疗剂反应不佳。因此他们需要更激烈的 导致副作用较差的治疗，当复发时，最常见的是致命的。 因此，不仅需要更多地强调T细胞癌的治疗剂，而且还需要 改善诊断的武器库以补充重点。 HRGR是一种新颖的癌基因 发现在许多T细胞癌中被突变和过表达。也已证明是 转化体外和动物模型。当灭活时，HRGR已被证明是反向的 T细胞恶性肿瘤的转变。 Omnicyte与纽约大学医学中心合作，计划开发预后的诊断，以进行预后 确定治疗选择，并补充小分子治疗的发展 针对HRGR。对于诊断，我们将尝试开发一种单克隆抗体 用于流式细胞仪（检测透化细胞中突变蛋白的存在）以及 单克隆抗体用于免疫组织化学。两种测定当前正在使用 血压恶性肿瘤的诊断和预后，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激活的癌基的测试。为了 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分析。 虽然我们开始开发治疗这些恶性肿瘤的治疗方法，但诊断测定是 至关重要的是分层临床试验的研究对象。此外，诊断将 对于可能受益于治疗性的患者的少数群体子集有必要。可能 更重要的是，该测定法可能提供预后信息，并可能指导用于 血液上的恶性肿瘤治疗，特别是为了避免复发和/或复发。这是我们的 渴望开发临床诊断以帮助癌症的临床诊断。有效 意识到我们努力的商业潜力我们希望享受诸如孤儿毒品状况的激励措施， 它提供赠款机会，FDA批准支持和7年市场的专有性。此外， 该公司已经开始利用基金会的支持和利他感兴趣的基金会支持 个人。最后，我们正在定位程序及其知识产权，以便它 当我们达到关键临床时，制药公司和其他机构投资者的兴趣 里程碑。