IGF::OT::IGF: SBIR PHASE II, TOPIC 326: DEVELOPMENT OF NOVEL THERAPEUTIC AGENTS THAT TARGET CANCER STEM CELLS

IGF::OT::IGF：SBIR 第二阶段，主题 326：开发针对癌症干细胞的新型治疗药物

• 批准号: 9361090
• 负责人: JAGATH JUNUTULA
• 金额: $ 149.63万
• 依托单位: CELLERANT THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-19 至 2018-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9361090
• 关键词: Affinity; Antibodies; Binding; Cells; Contractor; Contracts; Development; Effectiveness; Hematopoietic stem cells; Lead; Membrane; Patients; Pharmaceutical Preparations; Phase; Property; Rodent; Small Business Innovation Research Grant; Survival Rate; Technology; Therapeutic Agents; Toxic effect; Tumor Burden; base; cancer stem cell; cell growth; human tissue; leukemic stem cell; neoplastic cell; nonhuman primate; novel therapeutics; research study

The effectiveness of current AML treatments is abysmal yielding only an overall 5-year survival rate of ~25%, and it has been hypothesized that the treatment may be more durable if leukemic stem cells (LSC) are eliminated. IL1RAP is a compelling target because it is expressed on LSC in majority of AML patients, but not on healthy hematopoietic stem cells. Also, suppressing IL1RAP expression in AML cells can greatly inhibit tumor cell growth/survival. From SBIR Phase I contract, the contractor developed various antibodies against IL1RAP having functional blocking properties, a higher affinity for membrane-bound IL1RAP relative to the secreted form, and tumor cell inhibition activities.

目前AML治疗的有效性极差，仅产生约25%的总体5年生存率，并且已经假设如果消除白血病干细胞（LSC），则治疗可能更持久。IL 1 RAP是一个引人注目的靶点，因为它在大多数AML患者的LSC上表达，但在健康的造血干细胞上不表达。此外，抑制AML细胞中的IL 1 RAP表达可以极大地抑制肿瘤细胞生长/存活。 根据SBIR第一阶段合同，承包商开发了各种针对IL 1 RAP的抗体，这些抗体具有功能性阻断特性、相对于分泌形式对膜结合IL 1 RAP的更高亲和力以及肿瘤细胞抑制活性。