CD99 is a transmembrane glycoprotein shown to be upregulated in various malignancies. We have previously reported CD99 to be highly upregulated and present a viable therapeutic target in acute myeloid leukemia (AML). Currently, no therapy against CD99 is under clinical investigation. As a surface molecule, CD99 can be targeted with an antibody-based approach. Here, we have developed a new modality to target CD99 by engineering a fusion protein composed of a single-chain variable fragment antibody (anti-CD99 scFv) conjugated with a high molecular weight elastin-like polypeptide (ELP), A192: α-CD99-A192. This fusion protein assembles into multi-valent nanoworm with optimal physicochemical properties and favorable pharmacokinetic parameters (half-life: 16 h). α-CD99-A192 nanoworms demonstrated excellent in vitro and in vivo anti-leukemic effects. α-CD99-A192 induced apoptotic cell death in AML cell lines and primary blasts and prolonged overall survival of AML xenograft mouse model.

CD99 是一种跨膜糖蛋白，在多种恶性肿瘤中表达上调。我们之前曾报道 CD99 高度上调，是急性髓系白血病 (AML) 的可行治疗靶点。目前，尚无针对 CD99 的疗法正在进行临床研究。作为一种表面分子，CD99 可以通过基于抗体的方法进行靶向。在这里，我们开发了一种靶向 CD99 的新方式，通过设计由单链可变片段抗体（抗 CD99 scFv）与高分子量弹性蛋白样多肽（ELP）缀合的融合蛋白，A192：α-CD99 -A192。这种融合蛋白组装成多价纳米虫，具有最佳的理化特性和有利的药代动力学参数（半衰期：16小时）。 α-CD99-A192纳米虫在体外和体内表现出优异的抗白血病作用。 α-CD99-A192 诱导 AML 细胞系和原代母细胞凋亡，并延长 AML 异种移植小鼠模型的总体生存期。