Characterisation and development of 2448 and C51 : novel monoclonal antibodies targeting ovarian and breast cancer

• Main Author: Cua, Simeon
• Other Authors: Andre Choo
• Format: Theses and Dissertations
• Language: English
• Published: 2017
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: http://hdl.handle.net/10356/72381
• Institution: Nanyang Technological University

Monoclonal antibody (mAb) therapy represents an attractive targeted approach for the treatment of cancer. Nevertheless, only a limited number of antigens on solid tumours have been exploited. To address the diverse clinical spectrum of ovarian and breast cancer, the discovery of new antigen targets is needed. A panel of novel mAbs against human embryonic stem cells (hESC) was previously generated using a whole-cell immunisation approach in mice. Interestingly, many of these mAbs bind to oncofetal antigens that are expressed in a wide variety of cancers. From this panel, two mAbs, 2448 (IgG) and C51 (IgM), were selected, characterized and their anti-cancer activity investigated. Screening data showed that both mAbs target glycan-dependent epitopes on annexin A2 and can potentially monitor the Epithelial-Mesenchymal Transition (EMT) in ovarian and breast cancer. Functional studies using both in vitro and in vivo models elucidated various mechanisms of action which include direct tumor cell-killing and antibody-dependent cell-mediated cytotoxicity (ADCC). In addition, mAbs demonstrated efficient and specific cytotoxicity when conjugated to cytotoxic payloads as antibody drug conjugates (ADCs). Results indicate that 2448 and C51 are promising candidates for development as therapeutics.