Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA; Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Biomed Pharmacother. 2024 Oct;179:117265. doi: 10.1016/j.biopha.2024.117265. Epub 2024 Aug 20.
CD99 is a transmembrane protein overexpressed in Acute Myeloid Leukemia (AML), presenting a potential novel therapeutic target. Our group has previously developed anti-CD99-A192 (α-CD99-A192), comprising of single chain variable fragment (scFv) and elastin-like polypeptides (ELPs), and reported promising anti-leukemic activity in AML preclinical models. Treatment with α-CD99-A192 induced apoptosis in AML cell lines and prolonged survival in AML xenograft models. Considering CD99's expression and role in T cell activation, in the current study, we propose that α-CD99-A192 plays a dual function, i.e., targeting leukemic cells and activating T cells. This manuscript reports the effects of α-CD99-A192 on T cells in the context of AML. α-CD99-A192 treatment enhances T cell proliferation and activation and increases the release of pro-inflammatory cytokines along with increased aggregation of T cells, which culminates in heightened cytotoxicity against leukemic cells. Altogether, these findings suggest α-CD99-A192 enhances T cell activation and cytotoxic potential consistent with dual mechanisms of action for α-CD99-A192.
CD99 是一种在急性髓细胞白血病 (AML) 中过度表达的跨膜蛋白，是一种潜在的新型治疗靶点。我们的团队之前开发了抗 CD99-A192（α-CD99-A192），由单链可变片段（scFv）和弹性蛋白样多肽（ELPs）组成，并在 AML 临床前模型中报告了有希望的抗白血病活性。α-CD99-A192 治疗诱导 AML 细胞系凋亡，并延长 AML 异种移植模型的存活时间。鉴于 CD99 在 T 细胞激活中的表达和作用，在当前研究中，我们提出 α-CD99-A192 具有双重功能，即靶向白血病细胞和激活 T 细胞。本手稿报告了 α-CD99-A192 在 AML 背景下对 T 细胞的影响。α-CD99-A192 治疗增强了 T 细胞的增殖和激活，并增加了促炎细胞因子的释放，同时增加了 T 细胞的聚集，导致对白血病细胞的细胞毒性增强。总之，这些发现表明 α-CD99-A192 增强了 T 细胞的激活和细胞毒性潜能，与 α-CD99-A192 的双重作用机制一致。
