Development and assessments of cancer vaccines

The Tumour immunology group is run by Senior Research Scientist Dr Stephanie McArdle in the John van Geest Cancer Research Centre. Her group consists of postdoctoral researcher Dr Joshua Pearson, three PhD students and two MRes students.

Dr McArdle is a Senior Research Scientist in Tumour Immunology whose focus is on the development and pre-clinical assessment of T cell vaccines against cancers. Using HLA transgenic animals, her team evaluates the immunogenicity of cancer vaccines. Vaccines that prove successful are then assessed for their ability to prevent/slow down the growth of orthotopically implanted tumours in view of future human clinical trials. Immune-monitoring is also a focus, using techniques such as Flow cytometry, ELISPOT, NanoString and Cytokines detection to allow for a better understanding on immune cells involved in either the success or failure of the vaccine as well as their interactions with the tumour.

Dr McArdle has identified a mutated Prostatic Acid Phosphatase (PAP) derived sequence which she has investigated in collaboration with scientists at SSI, Denmark. She is also working on peptide sequences derived from WT1, HAGE and NY-ESO1 for the treatment of Triple Negative Breast Cancer (TNBC). HAGE has been shown to be a prognostic marker for breast cancer patients and a predictor of response to adjuvant chemotherapy in collaboration with scientists at NUH and the NHS Trust (Abel-Fateh T et al 2016, Abdel-Fateh T et al 2014).

Dr McArdle is also collaborating with Upsala University in Sweden and Ultimovacs AS in Norway to investigate immune responses against peptide sequences derived from the telomerase antigen. Many of the antigens that Dr McArdle is investigating can be used in other cancers too. Dr. McArdle also has a particular interest in the effect of exercise, mental health and gut microbiota on the immune system of cancer patients and a study is ongoing in prostate cancer patients to assess the level of inflammation related molecules, the psychological status and the gut permeability of prostate benign vs cancer patients in collaboration with scientists in the psychology department and clinicians at UHL NHS Trust, Leicester.

In addition to this, Dr McArdle is also collaborating with Scancell Ltd, investigating the potential use of a combined TRP2 and WT-1 vaccine for the treatment of Glioblastoma, which is funded by HeadCase.

Dr Pearson’s research focuses on harnessing the body’s own immune system to target GBM tumours. This is done by ‘educating’ the immune cells via vaccination with peptide targets expressed by GBM tumours. This therapeutic vaccination hones immune cells in on GBM tumours enabling them to mount an anti-tumour response. Unfortunately GBM tumours have numerous adaptations that enable them to evade immune attacks, and this often renders immunotherapies ineffective. The aim of this work is to combine active vaccination with immune modulating methods that help activated immune cells overcome the immunosuppressive barriers placed upon them by GBM tumours.

Recent collaborations:

• Dr Dennis Christensen, Head of vaccine adjuvant research. (Statens Serum Institute Denmark)
• Professor Lindy Durrant, Scientific Chief Officer, (Scancell Ltd, Nottingham, UK)
• Dr Sara Mangsbo, Chief Development Officer, (Ultimovacs AS, Norway)
• Dr Antoine Carpentier, Head of Neurology (University of Paris Decartes, France)
• Mr Masood Khan, Consultant Urologist (UHL NHS Trust, Leicester)

Prostate Cancer: Early Detection and Assessing Clinical Risk using Deep Machine Learning of High Dimensional Peripheral Blood Flow Cytometric Phenotyping Data. Georgina Cosma, Stephanie E.B. McArdle, Gemma A. Foulds, Simon P. Hood, Stephen Reeder, Catherine Johnson, Masood A. Khan, Alan Graham Pockley (2022). Frontiers in Immunology, accepted.

Synthesis and Functionalisation of Superparamagnetic Nano-Rods towards the Treatment of Glioblastoma Brain Tumours. Habra K, McArdle SEB, Morris RH, Cave GWV 2021. Nanomaterials (Basel). 11(9):2157. doi: 10.3390/nano11092157.

A Novel HAGE/WT1-ImmunoBody® Vaccine Combination Enhances Anti-Tumour Responses When Compared to Either Vaccine Alone Almshayakhchi R, Nagarajan D, Vadakekolathu J, Guinn BA, Reeder S, Brentville V, Metheringham R, Pockley AG, Durrant L, McArdle SE (2021). Front Oncol. 11:636977. doi: 10.3389/fonc.2021.636977.

Helicase antigen (HAGE)-derived vaccines induce immunity to HAGE and ImmunoBody®-HAGE DNA vaccine delays the growth and metastasis of HAGE-expressing tumors in vivo. Nagarajan D, Pearson J, Brentville V, Metheringham R, Pockley AG, Durrant L, McArdle SE (2021). Immunol Cell Biol. 99(9):972-989. doi: 10.1111/imcb.12485.

Cancer Vaccines: Adjuvant Potency, Importance of Age, Lifestyle, and Treatments. Cuzzubbo S, Mangsbo S, Nagarajan D, Habra K, Pockley AG, McArdle SEB (2021). Front Immunol. 11:615240. doi: 10.3389/fimmu.2020.615240.

Novel Combinatorial Approaches to Tackle the Immunosuppressive Microenvironment of Prostate Cancer. Shackleton EG, Ali HY, Khan M, Pockley GA, McArdle SE (2021). Cancers (Basel) 13(5):1145. doi: 10.3390/cancers13051145.

Reactive oxygen species as an initiator of toxic innate immune responses in retort to SARS-CoV-2 in an ageing population, consider N-acetylcysteine as early therapeutic intervention. Aikaterini Nasiai, Stephanie McArdle, Gustav Gaudernack, Gabriel Westman, Cornelis Melief, Johan Rockberg, Ramon Arens, Demetrios Kouretas, Jan Sjölin, Sara Mangsbo (2020). Toxicology Reports. 7:768-771.

Identifying prostate cancer and its clinical risk in asymptomatic men using machine learning of high dimensional peripheral blood flow cytometric natural killer cell subset phenotyping data. Simon P Hood, Georgina Cosma Is a corresponding author, Gemma A Foulds, Catherine Johnson, Stephen Reeder, Stéphanie E McArdle, Masood A Khan, A Graham. (2020). Pockley. eLife 9:e50936 DOI: 10.7554/eLife.50936.

Flow cytometry and targeted immune transcriptomics identify distinct profiles in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors with or without interferon-α. Alves, R., McArdle, S.E.B., Vadakekolathu, J. et al (2020). J Transl Med 18, 2 (2020); https://doi.org/10.1186/s12967-019-02194-x.

Immune Landscape of Breast Cancers. Nagarajan D, McArdle SEB. (2018). Biomedicines. 2018; 6(1):20. doi: 10.3390/biomedicines 6010020.

Immune-Phenotyping and Transcriptomic Profiling of Peripheral Blood Mononuclear Cells From Patients With Breast Cancer: Identification of a 3 Gene Signature Which Predicts Relapse of Triple Negative Breast Cancer. Foulds GA, Vadakekolathu J, Abdel-Fatah TMA, Nagarajan D, Reeder S, Johnson C, Hood S, Moseley PM, Chan SYT, Pockley AG, Rutella S, McArdle SEB (2018). Front Immunol. 2018; 9:2028. doi: 10.3389/fimmu.2018.02028. eCollection

Recent grant/contract capture:

Development of new immune-based treatments for Glioblastoma Multiforme (GBM)

Funding Body:                 Headcase Cancer Trust

Funding Period:               October 2019 – January 2022

Amount:                         £185,178

Towards the development of a new immunotherapy for the treatment of Glioblastoma multiforme (GBM)

Funding Body:                 Headcase Cancer Trust

Funding Period:               October 2015 – October 2018

Amount:                         £95,856

Assessing a novel PAP-derived vaccine for the treatment of advanced prostate cancer

Funding Body:                 Vice Chancellor Bursary Nottingham Trent University

Funding Period:               October 2015 – October 2018

Amount:                         £56,767 (Include only tuition fees)

Carnosine supplementation prior to vaccination restores vaccine-induced response in stress-induced inflammation settings: Implications for the efficacy of a cancer vaccine

Funding Body:                 Health and Wellbeing Theme, Nottingham Trent University

Funding period:               December 2016-July 2017

Amount:                         £19,0006 months

Co-Applicant

Genomic, proteomic, functional and therapeutic profiling of primed natural killer (NK) cell populations

Funding Body:                 INMune Bio International Ltd, UK

Funding Period:               May 2016 – July 2018

Amount:                         £268,615

The Tumour Immunology group currently houses a Gallios Flow Cytometer and a Cell Sorter together with the C.T.L. Elispot counter.

We have access within the John van Geest Cancer Research Centre to instrumentation which facilitates multi-omic analyses including gene expression micro-array, Nanostring platform, mass spectrometers and laser capture microdissection.