Oncotarget

Research Papers:

Targeting of embryonic annexin A2 expressed on ovarian and breast cancer by the novel monoclonal antibody 2448

Simeon Cua, Heng Liang Tan, Wey Jia Fong, Angela Chin, Ally Lau, Vanessa Ding, Zhiwei Song, Yuansheng Yang and Andre Choo _

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Oncotarget. 2018; 9:13206-13221. https://doi.org/10.18632/oncotarget.24152

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Abstract

Simeon Cua1, Heng Liang Tan1, Wey Jia Fong1, Angela Chin1, Ally Lau2, Vanessa Ding1, Zhiwei Song3, Yuansheng Yang4 and Andre Choo1,5

1Stem Cells 1 Group, Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore 138668, Singapore

2Proteomics Group, Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore 138668, Singapore

3Expression Engineering 1 Group, Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore 138668, Singapore

4Animal Cell Technology 1 Group, Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore 138668, Singapore

5Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore (NUS), Singapore 117575, Singapore

Correspondence to:

Andre Choo, email: andre_choo@bti.a-star.edu.sg

Keywords: annexin a2; antibody; antibody-dependent cell-mediated cytotoxicity; antibody drug conjugate; new targets

Received: November 06, 2017     Accepted: January 04, 2018     Published: January 10, 2018

ABSTRACT

Monoclonal antibodies (mAbs) play an increasingly important role in cancer therapy. To address the wide heterogeneity of the disease, the identification of novel antigen targets and the development of mAbs against them are needed. Our lab previously generated a panel of mAbs against human embryonic stem cells (hESC) using a whole cell immunization approach in mice. These mAbs can potentially target oncofetal antigens and be repurposed for antibody or antibody drug conjugate (ADC) therapy. From this panel, the novel IgG1 2448 was found to bind surface antigens on hESC and multiple cancer cell lines. Here, we show 2448 targets a unique glycan epitope on annexin A2 (ANXA2) and can potentially monitor the Epithelial-Mesenchymal Transition (EMT) in ovarian and breast cancer. To evaluate 2448 as a potential drug, 2448 was engineered and expressed as a chimeric IgG1. Chimeric 2448 (ch2448) demonstrated efficient and specific killing when conjugated to cytotoxic payloads as an ADC. In addition, ch2448 elicited potent antibody-dependent cell-mediated cytotoxicity (ADCC) activity in vitro and in vivo. Further engineering of ch2448 to remove fucose in the Fc domain enhanced ADCC. Overall, these findings indicate that embryonic ANXA2 is an attractive target and suggest that ch2448 is a promising candidate for further therapeutic development.


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