肿瘤细胞治疗研究
英文原题：Human antibodies targeting ENPP1 as candidate therapeutics for cancers.
外核苷酸焦磷酸酶/磷酸二酯酶 1（ENPP1）是一种在多种组织中表达的 II 型跨膜糖蛋白。
外核苷酸焦磷酸酶/磷酸二酯酶1（ENPP1）是一种在多种组织中表达的II型跨膜糖蛋白。肺癌、卵巢癌和乳腺癌等多种癌症中均观察到ENPP1高表达，且其过表达与这些疾病预后不良相关。因此，ENPP1是多种癌症免疫治疗的潜在靶点。本研究从大型噬菌体展示人源Fab抗体库中分离并表征了两种具有高亲和力和特异性的抗ENPP1 Fab候选抗体17和3G12。转化为IgG1后，由于亲合效应，两种抗体结合能力均显著增强。研究者基于这些抗体构建抗体药物偶联物（ADC）、IgG型双特异性T细胞衔接器（IbTE）和CAR T细胞，三者均能强效杀伤ENPP1表达细胞。因此，这些抗体衍生疗法是治疗人ENPP1表达型癌症的有前景候选方案。
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein expressed in many tissues. High expression levels of ENPP1 have been observed in many cancer types such as lung cancer, ovarian cancer, and breast cancer. Such overexpression has been associated with poor prognosis in these diseases. Hence, ENPP1 is a potential target for immunotherapy across multiple cancers. Here, we isolated and characterized two high-affinity and specific anti-ENPP1 Fab antibody candidates, 17 and 3G12, from large phage-displayed human Fab libraries. After conversion to IgG1, the binding of both antibodies increased significantly due to avidity effects. Based on these antibodies, we generated antibody-drug conjugates (ADCs), IgG-based bispecific T-cell engagers (IbTEs), and CAR T-cells which all exhibited potent killing of ENPP1-expressing cells. Thus, these various antibody-derived modalities are promising therapeutic candidates for cancers expressing human ENPP1.
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