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Title: Targeting of embryonic annexin A2 expressed on ovarian and breast cancer by the novel monoclonal antibody 2448
Authors: Cua, S
Tan, H.L
Fong, W.J
Chin, A
Lau, A
Ding, V
Song, Z 
Yang, Y
Choo, A 
Keywords: cytotoxic agent
immunoglobulin Fc fragment
immunoglobulin G1
lipocortin 2
monoclonal antibody
monoclonal antibody 2448
unclassified drug
animal experiment
animal model
animal tissue
breast cancer
cell mediated cytotoxicity
controlled study
drug conjugation
drug efficacy
drug potency
drug targeting
epithelial mesenchymal transition
human cell
in vitro study
in vivo study
ovary cancer
protein domain
protein engineering
protein expression
Issue Date: 2018
Publisher: Impact Journals LLC
Citation: Cua, S, Tan, H.L, Fong, W.J, Chin, A, Lau, A, Ding, V, Song, Z, Yang, Y, Choo, A (2018). Targeting of embryonic annexin A2 expressed on ovarian and breast cancer by the novel monoclonal antibody 2448. Oncotarget 9 (17) : 13206-13221. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
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 cellmediated 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. © Cua et al.
Source Title: Oncotarget
ISSN: 1949-2553
DOI: 10.18632/oncotarget.24152
Rights: Attribution 4.0 International
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