Abstract 6010: Evaluation of BsABN501: A novel T cell engager targeting CLDN3-positive solid tumors

Claudin 3 (CLDN3) plays a critical role in tumor initiation, progression, and metastasis and is overexpressed in multiple solid tumors, including breast, ovarian, and small cell lung cancers. Previously, ABN501 was developed as a fully human monoclonal antibody targeting CLDN3, demonstrating strong anti-tumor activity and a favorable safety profile. In this study, we established the proof of concept for BsABN501, a CD3 T cell engager, utilizing the anti-CLDN3 sequence derived from the novel antibody ABN501. BsABN501 specifically binds to CLDN3 while concurrently targeting CD3 on T cells, thereby initiating T cell-mediated cytotoxicity (TDCC) against tumor cells. In vitro assays demonstrated that BsABN501 effectively activates peripheral blood mononuclear cells, resulting in potent TDCC against CLDN3-positive cancer cell lines. Notably, BsABN501 exhibited robust cytotoxic activity against CLDN3-expressing tumor cell lines compared to controls. Cytokine release assays further confirmed tumor-specific activation of T cells. Additionally, in vivo studies using xenograft mouse models bearing CLDN3-expressing tumors showed that BsABN501 induced significant tumor regression, highlighting its robust anti-tumor activity. In summary, BsABN501 represents a novel and promising therapeutic strategy for the treatment of CLDN3-positivie solid tumors by effectively recruiting and activating T cells to enhance TDCC. Moving forward, we aim to optimize the CD3 sequence and format of BsABN501 to further improve its anti-cancer efficacy and safety, paving the way for its development as a targeted immunotherapeutic for CLDN3-expressing malignancies. Citation Format: Saehyung Lee, Sangin Lee, Sunghyun Hong, Jaemun Kim, Jae Choi, Hobin Yang, Sungyoul Hong, Na Young Kim, Jun Young Choi, Young Kee Shin. Evaluation of BsABN501: A novel T cell engager targeting CLDN3-positive solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6010.