Dr Frank Ward

Dr Frank Ward
Dr Frank Ward
Dr Frank Ward

GIBiol MIBiol PhD


Email Address
Telephone Number
+44 (0)1224 437358
Office Address
Office 5.18, Labs 4.51 & 1.16 Institute of Medical Sciences
Foresterhill Campus
Ashgrove Road West
AB25 2ZD

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School of Medicine, Medical Sciences and Nutrition

Research Overview

Understanding immunological tolerance is an important step towards developing new therapies for diseases that do not respond well to current treatments. Immunological tolerance can be described as the ability of the immune system to selectively recognise an antigen and choosing not to respond to it. For instance, our immune system usually will not attack tissues and cells of our own body but can recognise and respond to an infectious agent. This decision-making process is highly sophisticated but is heavily reliant on context and the presence or absence of danger signals that alert the immune system to the presence of a pathogen.

A full understanding of immunological tolerance will allow exquisite control over the immune system, switching responses on and off, according to the needs of the patient. For patients with autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and type 1 diabetes) selective intervention would allow effective disease treatment. A good example of such a therapy are the anti-cytokine therapies, which are now being used to treat psoriasis, while similar techniques could also control the immune responses underlying transplant rejection and even allergy.

Research Areas

Biomedical Sciences


Research Specialisms

  • Immunology
  • Medical Biotechnology

Our research specialisms are based on the Higher Education Classification of Subjects (HECoS) which is HESA open data, published under the Creative Commons Attribution 4.0 International licence.

Current Research

Immune checkpoints

Understanding immune tolerance can also be used to boost immunity and the last 10 years has seen this being exploited with some success to treat cancer. By removing immune checkpoints that suppress the adaptive immune response, the immune system can detect and destroy cancer cells anywhere in the body. Targeting these checkpoints is done using antibodies. In parallel with these clinical advances, we are also learning how cancers can escape the immune system and grow uncontrollably. As we learn of each escape mechanism, we can develop new therapies to shut them down. There are currently four checkpoint targets used to treat a broad range of cancers - CTLA-4, PD-1, PD-L1 and LAG-3.

Research interest and commercial development

The soluble isoform of CTLA-4 (sCTLA-4) is my focus of research for understanding tolerance. It also represents a target for checkpoint inhibitor immunotherapy. This less well-studied alternative isoform of the CTLA-4 receptor is produced by regulatory T cells, as well as cancer cells. It is important for driving reparative immune responses towards the end of an immune response but can also be used by cancer cells to evade and control the immune response.

Supported by a collection of global patents (see below), we developed a panel of high affinity antibodies specific for conformational epitopes on sCTLA-4. These antibodies bind both human and murine sCTLA-4 but not CTLA-4 receptor to selectively target sCTLA-4. We are currently seeking funding to take our lead candidate antibody into IND. Antibodies specific for sCTLA-4 have demonstrated anti-tumour activity but have the advantage that they do not rely on destruction of regulatory T cells, rendering them safer and applicable to any tumour types that produce or induce sCTLA-4 as part of an immune evasion strategy.

(Antibodies specifically directed to a soluble form of CTLA-4 https://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20140415&DB=EPODOC&locale=en_EP&CC=US&NR=8697845B2&KC=B2&ND=5)



Recent papers on soluble CTLA-4:

1.   Soluble CTLA-4 raises the threshold for T-cell activation and modulates anti-tumour immunity. Paul T. Kennedy, Emma L. Saulters, Andrew D. Duckworth, Yeong Jer Lim, John F. Woolley, Joseph R. Slupsky, Mark S. Cragg, Frank J. Ward, Lekh N. Dahal (bioRxiv 2023.06.05.543731; doi: https://doi.org/10.1101/2023.06.05.543731) Under review – tumour cells that produce sCTLA-4 are resistant to the cytotoxic effects of the immune system.

2.   Clare P, Al-Fatyan F, Risheh B, Nellany K, Ward FJ, Abu-Eid R. A Novel Role for the Soluble Isoform of CTLA-4 in Normal, Dysplastic and Neoplastic Oral and Oropharyngeal Epithelia. Cancers (Basel). 2023 Mar 10;15(6):1696. doi: 10.3390/cancers15061696. sCTLA-4 expression in epithelial cells to model stages of dysplastic growth associated with head and neck cancer.

3.    Khanolkar RC, Zhang C, Al-Fatyan F, Lawson L, Depasquale I, Meredith FM, Muller F, Nicolson M, Dahal LN, Abu-Eid R, Rajpara S, Barker RN, Ormerod AD, Ward FJ. TGFβ2 Induces the Soluble Isoform of CTLA-4 - Implications for CTLA-4 Based Checkpoint Inhibitor Antibodies in Malignant Melanoma. Front Immunol. 2022 Jan 5;12:763877. doi: 10.3389/fimmu.2021.763877.  sCTLA-4 in patients with malignant melanoma, providing evidence that TGFβ2 is an important factor for inducing sCTLA-4 expression by regulatory T cells.

4.   Dahal LN, Barker RN, Ward FJ. The Soluble Isoform of CTLA-4 Correlates with Interferon-α Activity in Systemic Lupus Erythematosus. J Rheumatol. 2020 Feb;47(2):302-304.

5.   Ward FJ, Dahal LN, Abu-Eid R. On the Road to Immunotherapy-Prospects for Treating Head and Neck Cancers With Checkpoint Inhibitor Antibodies. Front Immunol. 2018 Sep 24;9:2182. doi: 10.3389/fimmu.2018.02182. 

6.   Dahal LN, Schwarz H, Ward FJ. Hiding in Plain Sight: Soluble Immunomodulatory Receptors. Trends Immunol. 2018 Oct;39(10):771-774. doi: 10.1016/j.it.2018.08.004. Epub 2018 Sep 5.

7.   Dahal LN, Basu N, Youssef H, Khanolkar RC, Barker RN, Erwig LP, Ward FJ. Immunoregulatory soluble CTLA-4 modifies effector T-cell responses in systemic lupus erythematosus. Arthritis Res Ther. 2016 Aug 4;18:180. doi: 10.1186/s13075-016-1075-1. Role for sCTLA-4 in patients with systemic lupus erythematosus.

8.   Ward FJ, Dahal LN, Khanolkar RC, Shankar SP, Barker RN. Targeting the alternatively spliced soluble isoform of CTLA-4: prospects for immunotherapy? Immunotherapy. 2014;6(10):1073-84. doi: 10.2217/imt.14.73. 

9.   Ward FJ, Dahal LN, Wijesekera SK, Abdul-Jawad SK, Kaewarpai T, Xu H, Vickers MA, Barker RN. The soluble isoform of CTLA-4 as a regulator of T-cell responses. Eur J Immunol. 2013 May;43(5):1274-85. doi: 10.1002/eji.201242529. Epub 2013 Mar 6. First paper on sCTLA-4 blockade, showing it is immunosuppressive, produced in larger amounts by regulatory T cells and blocking its activity with antibody has anti-tumour activity in a model of melanoma.

Other recent papers:

  1. Abu-Eid R, Ward FJ. Targeting the PI3K/Akt/mTOR pathway: A therapeutic strategy in COVID-19 patients. Immunol Lett. 2021 Dec;240:1-8. doi: 10.1016/j.imlet.2021.09.005. Epub 2021 Sep 23. 
  2. O'Higgins C, Ward FJ, Abu Eid R. Deciphering the Role of Regulatory CD4 T Cells in Oral and Oropharyngeal Cancer: A Systematic Review. Front Oncol. 2018 Oct 15;8:442.
  3. Dahal LN, Hall LS, Barker RN, Ward FJ. Indoleamine 2,3 dioxygenase contributes to transferable tolerance in rat red blood cell inducible model of experimental autoimmune haemolytic anaemia. Clin Exp Immunol. 2013 Jul;173(1):58-66.

Past Research

Research over the last few years has focussed on antibody development in partnership with Aperio Pharma Ltd, and before that MRCT. The aim is to take a high affinity anti-sCTLA-4 antibody into clinical trials as a candidate checkpoint inhibitor with safety as a key USP.

We have also investigated the role of sCTLA-4 in patients with systemic lupus erythematous and in another study of melanoma. 


Currently collaborating with Dr Lekh N. Dahal at the University of Liverpool and Dr Rasha Abu-Eid at the Dental Institute, University of Aberdeen. 

Book:  Systemic Lupus Erythematosus: Methods and Protocols. Editors Dr P. Eggleton and Dr F.J.Ward. (2014) Humana Press.  ISBN-10 149390325X; ISBN-13 978-1493903252.