Effer Brian, Ulloa Daniel, Dappolonnio Camila, Muñoz Francisca, Iturrieta-González Isabel, Cotes Loraine, Rojas Claudio, Leal Pamela
Center of Excellence in Translational Medicine (CEMT) and Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco 4811230, Chile.
Carrera de Biotecnología, Facultad de Ciencias Agropecuarias y Medioambiente, Universidad de La Frontera, Temuco 4811230, Chile.
Antibodies (Basel). 2024 Mar 12;13(1):20. doi: 10.3390/antib13010020.
Gallbladder cancer (GBC) is a very aggressive malignant neoplasm of the biliary tract with a poor prognosis. There are no specific therapies for the treatment of GBC or early diagnosis tools; for this reason, the development of strategies and technologies that facilitate or allow an early diagnosis of GBC continues to be decisive. Phage display is a robust technique used for the production of monoclonal antibodies (mAbs) involving (1) the generation of gene libraries, (2) the screening and selection of isoforms related to an immobilized antigen, and (3) the in vitro maturation of the affinity of the antibody for the antigen. This research aimed to construct a human immune library from PBMCs of GBC patients and the isolation of clones with specificity against the larger extracellular loop belonging to claudin 18.2, which is an important biomarker overexpressed in GBC as well as gastric cancer. The immune-library-denominated GALLBLA1 was constructed from seven GBC patients and has a diversity of 6.12 × 10 mL. After three rounds of panning, we were able to identify clones with specificity against claudin 18.2. GALLBLA1 can contribute to the selection, isolation, and recombinant production of new human mAbs candidates for the treatment of gastrointestinal cancers.
胆囊癌（GBC）是一种侵袭性很强的胆道恶性肿瘤，预后较差。目前尚无治疗GBC的特异性疗法或早期诊断工具；因此，开发有助于或能够实现GBC早期诊断的策略和技术仍然至关重要。噬菌体展示是一种用于生产单克隆抗体（mAb）的强大技术，包括（1）基因文库的构建，（2）与固定化抗原相关的异构体的筛选和选择，以及（3）抗体对抗原亲和力的体外成熟。本研究旨在从GBC患者的外周血单核细胞（PBMC）构建人免疫文库，并分离出对claudin 18.2较大的细胞外环具有特异性的克隆，claudin 18.2是一种在GBC以及胃癌中过表达的重要生物标志物。以免疫文库命名的GALLBLA1由7名GBC患者构建而成，多样性为6.12×10 mL。经过三轮淘选，我们能够鉴定出对claudin 18.2具有特异性的克隆。GALLBLA1有助于筛选、分离和重组生产用于治疗胃肠道癌症的新型人源单克隆抗体候选物。
