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

Sep 21, 2026

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A therapeutic strategy targeting annexin-A1 (ANXA1) is evaluated using a humanised monoclonal antibody, MDX-124, in vitro and in vivo. The study provides a biological rationale by describing ANXA1 expression patterns in multiple cancers and its roles in proliferation, angiogenesis, invasion, immune regulation, and the tumour microenvironment. Results show that ANXA1 expression is detected across most tested human cancer cell lines and that MDX-124 reduces cancer cell proliferation in a dose-dependent manner. Subsequent in vivo assessment tests whether this growth inhibition translates beyond cell culture.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Introduction

ANXA1 biology and cancer relevance

Rationale for therapeutic inhibition

Results

ANXA1 expression and localisation in cancer cell lines

MDX-124 effects on in vitro proliferation

[www.nature.com/onc](www.nature.com/onc Oncogene)[ Oncogene](www.nature.com/onc Oncogene) BRIEF COMMUNICATION OPEN A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo Hussein N. Al-Ali1, Scott J. Crichton2, Charlene Fabian2, Chris Pepper 3, David R. Butcher 1, Fiona C. Dempsey2 and Christopher N. Parris 1 ✉ © The Author(s) 2024 INTRODUCTION Annexin-A1 (ANXA1) is a member of the annexin protein superfamily that bind to acidic phospholipids in a calciumdependent manner. ANXA1 is composed of a ‘core’ domain containing several repeating motifs and a unique ‘N-terminal’domain of approximately 43 residues in length. The core domain has a high degree of homology with other annexin family members and facilitates calcium-mediated binding to cell membranes, whilst the N-terminal domain confers many of the functional properties of ANXA1 [1] . ANXA1 is normally localised in the cytoplasm, however it can be secreted into the extracellular environment where it can modulate cell behaviour in an autocrine, paracrine or juxtacrine manner through the activation of formyl peptide receptors 1 and 2 (FPR1/2) [2] . Once secreted, ANXA1 is also susceptible to proteolytic cleavage generating fragments of the protein with differing biological activity [3, 4] . Much of the early literature describes ANXA1 as a pro-resolving mediator of inﬂammation [5] . However, more recently, a growing number of studies have suggested that ANXA1 can promote tumour development and progression [6, 7] . ANXA1 expression has been found to be increased in cancerous tissue versus adjacent or matched non-cancerous tissue in several tumour types including pancreatic [8], colorectal [9], lung [10] and gastric cancer [11], with high levels of ANXA1 expression often being associated with poor patient prognosis and lower overall survival [8, 11, 12] . In addition, high levels of ANXA1 expression are consistently observed in triple-negative breast cancer (TNBC), compared with other breast cancer subtypes [13–15], suggesting that it might bea promising therapeutic target in these tumours. The overexpression of ANXA1 by cancer cells has been demonstrated to increase cell proliferation [16], angiogenesis [17], migration/ invasion [18] and drug resistance [19] . ANXA1 has also been observed to inﬂuence immune cells and the tumour microenvironment by enhancing regulatory T-cell function [20], enhancing the polarisation and activation of M2 tumourassociated macrophages [21], suppressing dendritic cell activation and impairing CD8+ T-cell anti-tumour immunity [22] . Furthermore, ANXA1 is a key component of tumour-derived extracellular vesicles promoting migration, invasion and angiogenesis [23] and is secreted by cancer associated ﬁbroblasts increasing cancer stem cell generation [24] . In contrast, some studies have found downregulation of ANXA1 expression in cancers such as cervical and thyroid [25, 26] . Moreover, there are some subtypes of breast cancer where ANXA1 expression is reduced, with several studies reporting decreased ANXA1 expression in ductal carcinoma in situ and invasive ductal carcinoma compared to normal and benign tissues [13, 27] . These conﬂicting data suggest that the expression and function of ANXA1 as a tumour suppressor or a tumour promoter is regulated in a tissue and tumour-speciﬁc manner. There have been suggestions that the role of ANXA1 may be speciﬁc to each tumour type due to post-translational modiﬁcations of the protein impacting expression across a range of cell types or cancer indications [28] . As a result, further studies are needed to 1Anglia Ruskin University, School of Life Science, Faculty of Science and Engineering, East Road, Cambridge CB1 1PT, UK. 2Medannex Ltd, 1 Lochrin Square, 92-98 Fountainbridge, Edinburgh, Scotland EH3 9QA, UK. 3Brighton and Sussex Medical School, Medical Research Building, Falmer, Brighton BN1 9PX, UK. ✉ email: [Chris.parris@aru.ac.uk](Chris.parris@ar

FAQs

What is annexin-A1 (ANXA1) and why is it relevant to cancer?

ANXA1 is a calcium-dependent annexin protein involved in cell membrane binding and can be secreted and cleaved into fragments with different activities. Increased ANXA1 expression is linked to tumour progression and poorer prognosis in multiple cancer types, including triple-negative breast cancer.

How was ANXA1 expression and localisation assessed in the study?

Imaging flow cytometry was used to measure ANXA1 levels and determine cellular localisation in representative human cancer cell lines, showing cytoplasmic and plasma membrane localisation with minimal nuclear expression.

What effect does MDX-124 have on cancer cell proliferation in vitro?

MTT assays showed that MDX-124 significantly reduces proliferation in multiple ANXA1-expressing breast, pancreatic, ovarian, and colorectal cancer cell lines versus an IgG1 isotype control. The anti-proliferative response was dose-dependent across the tested concentration range.

Sep 21, 2026

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