CD99 是一种在 AML 中显着上调的受体。 FLT3-ITD AML 表现出更高水平的 CD99 表达。我们的团队之前采用了一种称为类弹性蛋白多肽的新型肽平台技术，并将其与能够结合 FLT3 (FLT3-A192) 或 CD99 (CD99-A192) 的单链抗体 (scFv) 融合。在 AML 小鼠模型中，使用 FLT3-A192 或 CD99-A192 靶向 FLT3 或 CD99 可导致 AML 细胞死亡并减少白血病负担。在这里，我们报告了一种能够结合 CD99 和 FLT3 的新型共组装构建体的开发，以及 FLT3-ITD AML 临床前模型中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）具有细胞毒性作用，可减少 FLT3-ITD AML 小鼠模型的白血病负担并延长生存期。总而言之，这项研究证明了针对 FLT3-ITD AML 中针对 FLT3 和 CD99 的创新治疗策略的潜力。

CD99 is a receptor that is significantly upregulated 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 (scFv) 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 to binding 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.