A new study published in the Nature Cancer Journal Oncogene underscores the effectiveness of MDX-124, the first therapeutic drug targeting Annexin-A1, a protein overexpressed in several types of cancer and promoting tumor progression.
The research was led by Professor Chris Parris and Dr. Hussein Al-Ali of Anglia Ruskin University (ARU) in collaboration with Professor Chris Pepper from the Brighton and Sussex Medical School and the British biotech company Medannex, which has developed the monoclonal antibody therapy MDX-124.
High levels of Annexin-A1 expression correlate with poorer overall survival in various types of cancer for which there are currently only limited treatment options, including triple-negative breast, pancreatic, colon, and prostate cancer.
The new study revealed that MDX-124, developed for use in immunotherapy, significantly reduces proliferation in a range of human cancer cell lines expressing Annexin-A1. This anti-proliferative effect is triggered by halting cell cycle progression.
Furthermore, it was demonstrated that MDX-124 significantly inhibits tumor growth in in vivo models of triple-negative breast and pancreatic cancer, indicating that Annexin-A1 targeted therapy represents a viable and innovative approach to cancer treatment.
Currently, the clinical phase-Ib study for MDX-124, named ATTAINMENT, is underway to determine the safety and optimal dose of the novel therapy. Its clinical efficacy will then be evaluated in newly diagnosed cancer patients in combination with current appropriate treatments.
We know that the protein Annexin-A1 activates formyl peptide receptors to initiate a complex network of intracellular signaling pathways that can lead to numerous cellular responses, including tumor initiation and progression.
In this new study, we have shown that the use of MDX-124 can reduce cell growth in Annexin-A1-expressing cancer cells both in vitro and in vivo, providing further evidence that Annexin-A1 is a valid target for cancer therapy.
Professor Chris Parris, Head of the School of Life Sciences at Anglia Ruskin University (ARU)
Dr. Fiona Dempsey, Director of Scientific Operations at Medannex and co-author of the paper, said: „We are pleased to publish this work with our collaborative partners, which demonstrates the anticancer potential of our innovative antibody therapeutic and look forward to publishing the clinical data from the ATTAINMENT study in due course.“
Al-Ali, HN, et al. (2024). A therapeutic antibody targeting Annexin-A1 inhibits cancer cell growth in vitro and in vivo. Oncogene. doi.org/10.1038/s41388-023-02919-9.