A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo

• Published in: Oncogene 2024-02, Vol.43 (8), p.608-614
• Main Authors: Al-Ali, Hussein N., Crichton, Scott J., Fabian, Charlene, Pepper, Chris, Butcher, David R., Dempsey, Fiona C., Parris, Christopher N.
• Format: Article
• Language: English
• Subjects: 13/1; 13/106; 13/31; 631/67; 631/67/1059/153; 82/80; Animal models; Animals; Annexin A1 - antagonists & inhibitors; Annexin A1 - metabolism; Antibodies; Apoptosis; Brief Communication; Cancer; Cell Biology; Cell cycle; Cell Line; Formyl peptide receptors; G1 phase; Human Genetics; Humans; Immunoglobulin G; Immunomodulation; Internal Medicine; Medicine; Medicine & Public Health; Mice; Monoclonal antibodies; Neoplasms; Oncology; Pancreatic cancer; Tumor cell lines
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/s41388-023-02919-9

In this study we conducted the first investigation to assess the efficacy of a novel therapeutic antibody developed to target annexin-A1 (ANXA1). ANXA1 is an immunomodulatory protein which has been shown to be overexpressed in, and promote the development and progression of, several cancer types. In particular, high ANXA1 expression levels correlate with poorer overall survival in pancreatic and triple-negative breast cancers, two cancers with considerable unmet clinical need. MDX-124 is a humanised IgG1 monoclonal antibody which specifically binds to ANXA1 disrupting its interaction with formyl peptide receptors 1 and 2 (FPR1/2). Here we show that MDX-124 significantly reduced proliferation ( p