Annexin-A1 targeted therapy beats several cancers

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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 tumor 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 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.

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.

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."

Professor Chris Parris, Head of School of Life Sciences at Anglia Ruskin University (ARU)

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."

Source:
Journal reference:

Al-Ali, H. N., 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.

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