A new study published in Nature’s cancer journal Oncogene highlights the effectiveness of MDX-124, the first therapeutic drug to target annexin-A1, a protein which is overexpressed in several cancer types and promotes tumour progression.
The research was led by Professor Chris Parris and Dr Hussein Al-Ali at Anglia Ruskin University (ARU) in collaboration with Professor Chris Pepper of Brighton and Sussex Medical School and UK biotech company Medannex, which has produced the MDX-124 monoclonal antibody therapy.
High annexin-A1 expression levels correlate with poorer overall survival in various cancers that currently have limited treatment options, including triple-negative breast, pancreatic, colorectal and prostate cancers.
The new study found that MDX-124, which is being developed for use in immunotherapy, significantly reduces proliferation across a number of human cancer cell lines expressing annexin-A1. This anti-proliferative effect is instigated by stopping cell cycle progression.
Additionally, MDX-124 is shown to significantly inhibit tumour 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.
The phase Ib clinical study of MDX-124, called ATTAINMENT, is currently underway to establish the safety and optimum dose of the novel therapy. Its clinical efficacy will then be evaluated in newly-diagnosed cancer patients, in combination with current appropriate treatments.
Professor Chris Parris, Head of School of Life Sciences at Anglia Ruskin University (ARU), said: “We know that the protein annexin-A1 activates formyl peptide receptors to initiate a complex network of intracellular signalling pathways, which can lead to numerous cellular responses, including tumour initiation and progression.
“We have demonstrated in this new study that using 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 therapy in cancer.”
Medannex Director of Scientific Operations, Dr Fiona Dempsey, who co-authored the paper, said: “We are delighted to publish this work with our collaborators demonstrating the anti-cancer potential of our innovative antibody therapeutic and look forward to the clinical data coming out of the ATTAINMENT study in due course.”
The open access Oncogene paper is available here: https://www.nature.com/articles/s41388-023-02919-9
Details of the ATTAINMENT clinical study can be accessed here: https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-mdx-124-for-solid-tumours-that-have-spread-attainment
Journal
Oncogene
Method of Research
Randomized controlled/clinical trial
Subject of Research
Cells
Article Title
A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo