PDF(Pubmed)
Abstract：
Cluster of differentiation 99 (CD99) is a receptor that is significantly upregulated in acute myeloid leukemia (AML). FMS-like tyrosine kinase 3 internal tandem duplication mutation in AML (FLT3-ITD AML) exhibits even higher levels of CD99 expression. Our group previously employed a novel peptide platform technology called elastin-like polypeptides and fused it with single-chain antibodies capable of binding to FLT3 (FLT3-A192) or CD99 (CD99-A192). Targeting either FLT3 or CD99 using FLT3-A192 or CD99-A192 led to AML cell death and reduced leukemia burden in AML mouse models. Here, we report on the development of a novel Co-Assembled construct that is capable of binding to both CD99 and FLT3 and the antileukemia activity of the bispecific construct in FLT3-ITD AML preclinical models. This dual-targeting Co-Assembled formulation exhibits cytotoxic effects on AML cells (AML cell lines and primary blasts) and reduced leukemia burden and prolonged survival in FLT3-ITD AML mouse models. Altogether, this study demonstrates the potential of an innovative therapeutic strategy that targets both FLT3 and CD99 in FLT3-ITD AML.
UNASSIGNED: This study investigates a dual-targeting strategy in acute myeloid leukemia (AML), focusing on FLT3 and CD99. The approach demonstrates enhanced therapeutic potential, presenting a novel option for AML treatment.
UNASSIGNED: This study investigates a dual-targeting strategy in acute myeloid leukemia (AML), focusing on FLT3 and CD99. The approach demonstrates enhanced therapeutic potential, presenting a novel option for AML treatment.
摘要：
CD99是在AML中显著上调的受体。FLT3-ITDAML表现出甚至更高水平的CD99表达。我们的团队先前采用了一种称为弹性蛋白样多肽的新型肽平台技术，并将其与能够结合FLT3（FLT3-A192）的单链抗体（scFv）融合。或CD99（CD99-A192）。使用FLT3-A192或CD99-A192靶向FLT3或CD99导致AML小鼠模型中的AML细胞死亡和降低的白血病负担。这里,我们报道了在FLT3-ITDAML临床前模型中能够同时结合CD99和FLT3的新型共组装构建体的开发以及双特异性构建体的抗白血病活性.这种双靶向共组装制剂对AML细胞(AML细胞系和原代母细胞)表现出细胞毒性作用,并在FLT3-ITD小鼠模型中降低白血病负荷和延长存活。总之,这项研究证明了在FLT3-ITDAML中靶向FLT3和CD99的创新治疗策略的潜力.
