Angiocidin, a Novel Differentiation Agent for the Treatment of Leukemia

描述（由申请人提供）：该1期SBIR项目是对专利蛋白血管杀虫素（angiocidin）作为治疗急性髓性白血病（AML）的新疗法进行进行/不进行评估。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有效率低，并且在许多老年人中是禁忌的，而老年人是AML患者中最大和增长最快的人群。血管杀菌素，其作用模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。分化治疗是一个被充分研究的概念

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.