Angiocidin, a Novel Differentiation Agent for the Treatment of Leukemia

血管抑制素，一种治疗白血病的新型分化剂

• 批准号: 8521797
• 负责人: CHARLES S SWINDELL
• 金额: $ 28.83万
• 依托单位: DIFFREGEN, LLC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-17 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8521797
• 关键词: 1-Phosphatidylinositol 3-Kinase; Acute Lymphocytic Leukemia; Acute Myelocytic Leukemia; Acute Promyelocytic Leukemia; Acute T Cell Leukemia; Acute leukemia; Address; Adult; Adverse effects; Advocacy; Agar; Age; Agreement; Animal Model; Animals; Area; Arsenic Trioxide; Automobile Driving; Avastin; Biological; Blast Cell; Businesses; CD14 gene; Cancer cell line; Caring; Cell Line; Cells; Child; Cities; Clinical; Clinical Research; Clinical Trials; Combined Modality Therapy; Cytarabine; Cytotoxic agent; Data; Data Set; Daunorubicin; Development; Differentiation Inducer; Differentiation Therapy; Dose; Drug usage; Elderly; Endostatins; Escherichia coli; Evaluation; Feasibility Studies; Fibroblast Growth Factor 2; Foundations; Funding; Future; Goals; Grant; Growth; Human; ICAM1 gene; In Vitro; Incidence; Intellectual Property; Interleukin-6; Knowledge; Leukemic Cell; Local Government; Macrophage-1 Antigen; Marketing; Maximum Tolerated Dose; Mediation; Medical; Mitogen-Activated Protein Kinase 3; Modeling; Mono-S; Morphology; Multi-Drug Resistance; Mus; Nude Mice; Outcome; Pathway interactions; Patients; Pennsylvania; Performance; Pharmacologic Substance; Pharmacology and Toxicology; Phase; Phenotype; Philadelphia; Population; Prevalence; Production; Property; Proteins; Recombinants; Research; SCID Mice; Safety; Sales; Science; Series; Small Business Innovation Research Grant; Solid Neoplasm; Specialist; Specimen; Staging; Survival Rate; Treatment outcome; Tretinoin; Tumor-Derived; Universities; Vascular Endothelial Growth Factors; Work; angiogenesis; base; bevacizumab; cell bank; cohort; commercialization; cytokine; experience; improved; in vivo; inhibitor/antagonist; leukemia; macrophage; man; meetings; monocyte; novel; oncology; pre-clinical; preclinical efficacy; product development; programs; public health relevance; research study; safety study; standard of care; subcutaneous; success; therapeutic protein; tumor; tumor growth

DESCRIPTION (provided by applicant): This Phase 1 SBIR project is to perform go-/no-go evaluation of the proprietary protein, angiocidin, as a novel therapy for the treatment of acute myeloid leukemia (AML). AML is a significant medical burden as existing therapy based on cytotoxic drugs has a low efficacy rate and is contraindicated in many elderly people, who comprise the largest and fastest growing population of AML patients. Angiocidin, whose mode of action is to drive differentiation of leukemic blast cells, has the potential to revolutionize leukemia therapy, especially in the elderly. Differentiation therapy is a well-investigated concept in AML. This has been driven by the dramatic clinical success of differentiation agents (ATRA and arsenic trioxide) in acute promyelocytic leukemia (APL), a subtype of AML. Unfortunately, the remaining AML subtypes do not respond to these agents or others which are mechanistically similar. The work of Diffregen and its consortium partner, Temple University, has demonstrated angiocidin's ability to drive differentiation of leukemic cells in vitro and has begun to elucidate the novel mechanism of this activity. Here we are proposing a series of animal studies to evaluate the in vivo utility of angiocidin as a differentiation agent for AML. Feasibility work will focus on three areas: (1) establish a foundation for manufacturing angiocidin for proof-of-feasibility studies and for future GMP work; (2) evaluate angiocidin's efficacy, alone and in combination with standard of care cytotoxic drugs, in an animal model regularly used by drug developers to evaluate the performance of new AML therapies; (3) broaden our knowledge of angiocidin's utility in other acute leukemias in an animal model of acute lymphocytic leukemia (ALL). ALL is an important extension of angiocidin's potential utility because despite the success of standard of care in children, adults with ALL have the same poor outcomes as patients with AML. Successful completion of Diffregen's planned studies will provide the preclinical efficacy data needed to support the initiation of IND- directed development work and progression toward clinical studies in man, and will establish the dataset required to make educated decisions on the commercial viability of the product.

描述（由申请人提供）：该1期SBIR项目是对专利蛋白质angiocidin作为治疗急性髓性白血病（AML）的新型疗法进行go-/no-go评价。AML是一个重大的医疗负担，因为现有的基于细胞毒性药物的治疗具有低疗效率，并且在许多老年人中是禁忌的，而老年人构成了AML患者的最大和增长最快的人群。血管杀菌素，其作用方式是驱动白血病母细胞分化，有可能彻底改变白血病治疗，特别是在老年人中。分化治疗是一个研究充分的概念 在AML。这是由于分化剂（ATRA和三氧化二砷）在急性早幼粒细胞白血病（APL）（AML的一种亚型）中取得了巨大的临床成功。不幸的是，其余的AML亚型对这些药物或其他机制相似的药物没有反应。Diffregen及其合作伙伴坦普尔大学的工作已经证明了血管杀菌素在体外驱动白血病细胞分化的能力，并开始阐明这种活性的新机制。在这里，我们提出了一系列的动物研究，以评估在体内效用的血管杀菌素作为分化剂的AML。可行性工作将集中在三个方面：（1）建立生产血管杀菌素的基础 用于可行性验证研究和未来的GMP工作;（2）单独评估血管杀菌素的疗效 并与标准治疗细胞毒性药物组合，在药物开发人员经常使用的动物模型中评估新AML疗法的性能;（3）在急性淋巴细胞白血病（ALL）的动物模型中拓宽我们对血管杀菌素在其他急性白血病中的效用的认识。ALL是血管杀菌素潜在效用的重要延伸，因为尽管儿童标准治疗取得了成功，但成人ALL患者的结局与AML患者相同。成功完成Diffregen计划的研究将提供支持IND指导的开发工作和人类临床研究进展所需的临床前疗效数据，并将建立对产品商业可行性做出明智决策所需的数据集。