Ruiz-Ciancio Dario, Lin Li-Hsien, Veeramani Suresh, Barros Maya N, Sanchez Diego, Di Bartolo Ary Lautaro, Masone Diego, Giangrande Paloma H, Mestre María Belén, Thiel William H
Instituto de Ciencias Biomédicas (ICBM), Facultad de Ciencias Médicas, Universidad Católica de Cuyo, Av. José Ignacio de la Roza 1516, Rivadavia, San Juan 5400, Argentina.
National Council of Scientific and Technical Research (CONICET), Godoy Cruz 2290, Ciudad Autónoma de Buenos Aires C1425FQB, Argentina.
Mol Ther Nucleic Acids. 2023 Jul 28;33:698-712. doi: 10.1016/j.omtn.2023.07.028. eCollection 2023 Sep 12.
Despite improvements in B cell acute lymphoblastic leukemia (B-ALL) treatment, a significant number of patients experience relapse of the disease, resulting in poor prognosis and high mortality. One of the drawbacks of current B-ALL treatments is the high toxicity associated with the non-specificity of chemotherapeutic drugs. Targeted therapy is an appealing strategy to treat B-ALL to mitigate these toxic off-target effects. One such target is the B cell surface protein CD22. The restricted expression of CD22 on the B-cell lineage and its ligand-induced internalizing properties make it an attractive target in cases of B cell malignancies. To target B-ALL and the CD22 protein, we performed cell internalization SELEX (Systematic Evolution of Ligands by EXponential enrichment) followed by molecular docking to identify internalizing aptamers specific for B-ALL cells that bind the CD22 cell-surface receptor. We identified two RNA aptamers, B-ALL1 and B-ALL2, that target human malignant B cells, with B-ALL1 the first documented RNA aptamer interacting with the CD22 antigen. These B-ALL-specific aptamers represent an important first step toward developing novel targeted therapies for B cell malignancy treatments.
尽管B细胞急性淋巴细胞白血病（B-ALL）的治疗取得了进展，但仍有相当数量的患者出现疾病复发，导致预后不良和高死亡率。当前B-ALL治疗方法的缺点之一是与化疗药物的非特异性相关的高毒性。靶向治疗是治疗B-ALL以减轻这些毒性脱靶效应的一种有吸引力的策略。其中一个这样的靶点是B细胞表面蛋白CD22。CD22在B细胞谱系上的限制性表达及其配体诱导的内化特性使其成为B细胞恶性肿瘤病例中的一个有吸引力的靶点。为了靶向B-ALL和CD22蛋白，我们进行了细胞内化SELEX（指数富集配体系统进化），然后进行分子对接，以鉴定与CD22细胞表面受体结合的、对B-ALL细胞具有特异性的内化适体。我们鉴定出了两种RNA适体，B-ALL1和B-ALL2，它们靶向人类恶性B细胞，其中B-ALL1是首个有文献记载的与CD22抗原相互作用的RNA适体。这些B-ALL特异性适体是朝着开发用于B细胞恶性肿瘤治疗的新型靶向疗法迈出的重要的第一步。
