可以利用胚胎细胞和恶性细胞之间的分子相似性，通过健康成人组织中不存在的特定特征来靶向肿瘤。其中一种胚胎特征肿瘤表达的是癌胎儿硫酸软骨素（ofCS），它支持癌症的疾病进展和传播。在这里，我们报告了识别两个不同的 CS 表位的噬菌体展示衍生抗体片段的鉴定和表征。这些抗体片段在体外和体内多种实体瘤类型中显示出低纳摩尔范围内的 ofCS 结合亲和力，与正常、发炎或良性肿瘤组织的结合最小。基于这些靶向部分的抗-ofCS抗体药物缀合物和双特异性免疫细胞接合剂可破坏人类和小鼠癌症动物模型中的肿瘤进展。因此，抗-ofCS 抗体片段有望开发针对人类恶性肿瘤的广泛有效的治疗和诊断应用。© 2024。作者。

Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes. These antibody fragments show binding affinity to ofCS in the low nanomolar range across a broad selection of solid tumor types in vitro and in vivo with minimal binding to normal, inflamed, or benign tumor tissues. Anti-ofCS antibody drug conjugates and bispecific immune cell engagers based on these targeting moieties disrupt tumor progression in animal models of human and murine cancers. Thus, anti-ofCS antibody fragments hold promise for the development of broadly effective therapeutic and diagnostic applications targeting human malignancies.© 2024. The Author(s).