Abstract
Abstract CD44 is a transmembrane glycoprotein that binds to the extracellular matrix including hyaluronic acid. Human CD44 has 19 exons, 10 of which are commonly present in all isoforms. CD44 standard isoform (CD44s) is composed of the common exons, and is expressed in many cell types. CD44 variants (CD44v) are produced by alternative splicing, in which the remaining nine variant exons are inserted into the CD44 standard isoform in various combinations. The CD44 isoforms have overlapping and unique functions. Both CD44s and CD44v harbor hyaluronan-binding motifs that promote interaction with the tumor microenvironment, which activate various signaling pathways in tumor cells. CD44v is mainly expressed in epithelial cells and is involved in cell adhesion, proliferation, and survival. Overexpression of CD44v is observed in many solid tumors and plays an important role in invasion, metastasis, and acquisition of stemness. In this study, we employed the Cell-Based Immunization and Screening method (CBIS method), and established highly sensitive anti-CD44 monoclonal antibodies (mAbs) using CD44v3-10-overexpressed cell lines as immunogens. After that, we determined the epitopes by enzyme-linked immunosorbent assay and investigated their applications. As a result, we successfully established eight mAbs against each CD44v (v3 to v10), which can be used for flow cytometry, western blotting, and immunohistochemistry. Furthermore, some of them exhibited cancer specificity against pancreatic cancers, colorectal cancers, gastric cancers, or oral cancers, indicating that established anti-CD44v mAbs are useful for the antibody therapies. Citation Format: Yukinari Kato, Hiroyuki Suzuki, Mika K. Kaneko. Development of monoclonal antibodies against CD44v specifically expressed in cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1857.
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