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

目前AML治疗的有效性非常糟糕，总体5年生存率仅为25%，并且假设如果消除白血病干细胞（LSC），治疗可能会更持久。IL1RAP是一个引人注目的靶标，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IL1RAP的表达可以极大地抑制肿瘤细胞的生长/存活。从SBIR I期合同开始，承包商开发了多种针对IL1RAP的抗体，这些抗体具有功能性阻断特性，相对于分泌形式，对膜结合的IL1RAP具有更高的亲和力，并且具有肿瘤细胞抑制活性。

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.