In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 311-311
Abstract:
The tight junctions of epithelial tissues, that most malignant tumors are derived from, are associated in cell-cell interactions. Among the tight junction proteins, claudin-3 (CLDN3) is overexpressed in many types of solid cancers, such as breast, ovarian, colorectal, and gastric cancers. Although CLDN3 can be potential therapeutic target due to the overexpression in various types of cancers, high homology with other CLDN family members is a hurdle to develop antibodies specifically targeting CLDN3. In this study, human IgG1 monoclonal antibody (ABN501) against CLDN3 was developed by scFv phage display using CLDN3-overexpressing stable cells and CLDN3-embedded lipoparticles as antigens. It was confirmed that ABN501 specifically bound to human and mouse CLDN3 without cross-reactivity to other CLDN family members. Sub-nanomolar affinity in binding kinetics of ABN501 was measured in CLDN3 expressing cell lines. We observed the antibody-dependent cytotoxicity (ADCC) activity of ABN501 with human NK cells expressing CD16a (NK-92MI-CD16a), in various cancer cell lines according to CLDN3 expression levels. We also confirmed that ABN501 specifically targeted CLDN3-expressing tumors in biodistribution assay using fluorescence-conjugated ABN501. In addition, ABN501 showed anti-tumor effects when treated with NK-92MI-CD16a in xenograft mice bearing CLDN3 expressing tumors. Taken these results together, we suggest that ABN501, specifically recognizing to CLDN3, can be used as therapeutic agents for CLDN3 positive cancer, and developed in many different forms to treat cancers with its specificity for cancer diagnosis, antibody-drug conjugates, and chimeric antigen receptor (CAR) immunotherapy. Citation Format: Hong-Seok Choi, Euni Sim, Na Young Kim, Yong Jin Lee, Sae Hyung Lee, Hayeon Park, Hobin Yang, Jiwon Jo, Myeung-Ryun Seo, Heegeon Park, Ji-Hye Lee, Sungyoul Hong, Young Kee Shin, Jun-Young Choi. Development of cludin-3 specific human monoclonal antibody(ABN501) as therapeutic anti-tumor agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 311.
Type of Medium:
Online Resource
ISSN:
1538-7445
DOI:
10.1158/1538-7445.AM2022-311
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2022
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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