Abstract 2653: ABN501, a novel anti-claudin-3 antibody, shows potent anti-cancer activity in vitro and in vivo

Abstract

Abstract Claudin-3, one of the tight junction proteins, could be a potential therapeutic target and biomarker. Since it is not only overexpressed in various types of malignant solid cancers but also exposed externally during tumorigenesis. Previously, we developed a fully human monoclonal antibody (ABN501) with sub-nanomolar affinity against the native claudin-3 protein. In this study, we confirmed that ABN501 is highly specific for the extracellular loop (ECL) 2 domain of claudin-3 using stable cell lines expressing two chimeric claudins fused to claudin-3 and claudin-4. Followed by, we evaluated in vitro ADCC activity of ABN501 using NK cells expressing CD16a (NK-92MI-CD16a), in various cancer cell lines, expressing claudin-3. ABN501 exhibited potent in vitro ADCC activity in diverse cancer cell lines. We also confirmed in vivo anti-tumor activity of ABN501 in xenograft mice bearing claudin-3-expressing tumors. In summary, we suggest that ABN501 can be used as promising tissue-agnostic drug candidates as therapeutics for various types of claudin-3-positive cancers. ABN501 is currently developed with various antibody engineering platforms. Citation Format: Saehyung Lee, Jae Choi, Sunghyun Hong, Euni Sim, Jaemun Kim, Sangin Lee, Sungyoul Hong, Hobin Yang, Jiwon Jo, Na Young Kim, Young Kee Shin, Jun Young Choi. ABN501, a novel anti-claudin-3 antibody, shows potent anti-cancer activity in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2653.