Dr Steven Lee BSc, PhD

Steven Lee

Institute of Immunology and Immunotherapy
Senior Research Fellow

Contact details

Address
Institute of Immunology and Immunotherapy
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Steven Lee is a Senior Research Fellow in the Institute of Immunology and Immunotherapy. He has over 25 years experience of working on cellular immune responses to viruses and human cancer with particular emphasis on Epstein-Barr virus-associated tumours and targeting the tumour vasculature with engineered CAR-T cells. He is an enthusiastic communicator and teacher on the theme of immune-based therapies for cancer presenting his work to both academics and the general public.

Qualifications

  • Senior Research Fellow
  • PhD in Immunology, University of London 1990
  • BSc (Hons) in Microbiology, University of Bristol 1986

Biography

Steven Lee qualified with a BSc (Hons) in Microbiology from the University of Bristol in 1986. He went on to study for a PhD at the London School of Hygiene and Tropical Medicine researching immune responses in leprosy patients.

In 1989 he joined the Institute of Cancer Studies at the University of Birmingham. After a couple of post-doc positions, he received a Career Development Award from the MRC which afforded the opportunity to spend a year working in the laboratory of Prof Philip Greenberg at the Fred Hutchinson Cancer Research Center, Seattle, USA.

Upon returning to Birmingham, Steven obtained a Senior Cancer Research Fellowship from Cancer Research UK and was successful in renewing this Fellowship in 2006. Throughout his time in Birmingham he has studied the immune response to Epstein-Barr virus (EBV) and EBV-associated human cancers.  He is now focussing on genetic engineering of T cells to target both virus- and non-virus-associated cancers with a particular interest in targeting the tumour vasculature.

Teaching

Postgraduate supervision

Steven is interested in supervising doctoral research students in the following areas:

• Immune responses to viruses and human cancer
• Immune-based therapies for human cancer

If you are interesting in studying any of these subject areas please contact Steven on the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.

Research

T cell therapy for human cancers

Antibodies for cancer therapy are already in clinical use, but T cells offer even greater potential in this context because of their ability to recognise intracellular antigens. Our laboratory is seeking to develop T cell therapy for human cancer using genetic engineering approaches to attack the malignant cells directly (e.g. targeting viral antigens known to be expressed in some cancers) or by attacking the tumour vasculature upon which the cancer depends. We are currently engaged in preclinical development of some of these therapies which we plan to take forward to clinical testing in phase I trials.

Epstein-Barr virus (EBV)-associated malignancies

Through a well-established collaboration with the Chinese University of Hong Kong (Prof. A.T.C. Chan, Prof. K.W. Lo) we have investigated T cell responses to the undifferentiated form of Nasopharyngeal carcinoma (NPC), one of the most common cancers in South East Asia and one that is consistently EBV-positive. Alongside our basic research into the immunology of this cancer, including the definition of viral target antigens, immune evasion mechanisms and the function of T cells that naturally reside within the tumour tissue, we are developing adoptive T cell therapy approaches.

T cell receptor (TCR) gene transfer

We have successfully cloned genes encoding a TCR specific for LMP2, an EBV protein widely expressed in NPC. Using retroviral mediated gene transfer we have then delivered this TCR into T cells. The result is that within 3-5 days we can reliably generate large numbers of high avidity LMP2-specific effectors capable of recognising cells endogenously expressing physiological levels of this viral protein. We are currently designing a phase I trial in which to test these modified T cells in NPC patients.

Chimeric antigen receptors (CARs) targeting the tumour vasculature 

A major focus of our current work is the use of CARs.  These combine the specificity of antibodies with the cytotoxic and immunomodulatory functions of T cells and function in an MHC-unrestricted manner. Typically, CARs consist of a single chain variable fragment (scFv) of a specific antibody linked to intracellular T cell signalling domains. Working with Prof Roy Bicknell (University of Birmingham) we have identified several tumour endothelial markers and are exploring their suitability as targets for CAR-based T cell therapies.  One of these markers, CLEC14A, is highly expressed on the surface of endothelial cells lining the vasculature of many common human cancers but is poorly expressed/undetectable in the vasculature of healthy tissue. CARs targeting this marker have yielded encouraging results both in vitro and in vivo and we are currently working with the Cell and Gene Therapy Catapult in preclinical development of this approach leading towards a phase I clinical trial.

Other activities

  • Radiation Protection Supervisor (RPS) for the Institute.
  • Training Lead for the CRUK Birmingham Cancer Centre.

Publications

Recent publications

Article

Petrovic, K, Robinson, J, Whitworth, K, Jinks, E, Shaaban, A & Lee, S 2019, 'TEM8/ANTXR1-specific CAR T cells mediate toxicity in vivo', PLoS ONE, vol. 14, no. 10, e0224015. https://doi.org/10.1371/journal.pone.0224015

Brooks, J, Antao Mobre De Menezes, ARE, Ibrahim, M, Archer, L, Lal, N, Bagnall, C, Zeidler, SVV, Valentine, H, Spruce, R, Batis, N, Bryant, J, Hartley, M, Kaul, B, Ryan, G, Bao, R, Khattri, A, Lee, S, Ogbureke, KUE, Middleton, G, Tennant, D, Beggs, A, Deeks, J, West, CML, Cazier, J-B, Willcox, B, Seiwert, TY & Mehanna, H 2019, 'Development and validation of a combined hypoxia and immune prognostic classifier for head and neck cancer', Clinical Cancer Research, vol. 25, no. 17, pp. 5315-5328. https://doi.org/10.1158/1078-0432.CCR-18-3314

Noy, PJ, Gavin, RL, Colombo, D, Haining, EJ, Reyat, JS, Payne, H, Thielmann, I, Lokman, AB, Neag, G, Yang, J, Lloyd, T, Harrison, N, Heath, VL, Gardiner, C, Whitworth, KM, Robinson, J, Koo, CZ, Di Maio, A, Harrison, P, Lee, SP, Michelangeli, F, Kalia, N, Rainger, GE, Nieswandt, B, Brill, A, Watson, SP & Tomlinson, MG 2019, 'Tspan18 is a novel regulator of the Ca2+ channel Orai1 and von Willebrand factor release in endothelial cells', Haematologica, vol. 104, no. 9, pp. 1892-1905. https://doi.org/10.3324/haematol.2018.194241

Knoblich, K, Cruz Migoni, S, Siew, S, Jinks, E, Kaul, B, Jeffery, H, Baker, A, Suliman, M, Vrzalikova, K, Mehanna, H, Murray, P, Barone, F, Newsome, P, Hirschfield, G, Kelly, D, Oo, YH, Lee, S, Parekkadan, B, Turley, S & Fletcher, A 2018, 'The human lymph node microenvironment unilaterally regulates T cell activation and differentiation', PLoS Biology. https://doi.org/10.1371/journal.pbio.2005046

Tubb, V, Schrikkema, D, Croft, N, Purcell, A, Linnemann, C, Freriks, M, Chen, F, Long, H, Lee, S & Bendle, G 2018, 'Isolation of T cell receptors targeting recurrent neoantigens in hematological malignancies', Journal for ImmunoTherapy of Cancer, vol. 6, 70. https://doi.org/10.1186/s40425-018-0386-y

Zheng, Y, Parsonage, G, Zhuang, X, Machado, LR, James, CH, Salman, A, Searle, PF, Hui, EP, Chan, ATC & Lee, SP 2015, 'Human Leukocyte Antigen (HLA) A*1101-restricted Epstein-Barr virus-specific T-cell receptor gene transfer to target Nasopharyngeal carcinoma: TCR gene transfer to target NPC', Cancer immunology research. https://doi.org/10.1158/2326-6066.CIR-14-0203-T

Zhuang, X, Kaul, B, Bentley, M, Nagy, Z, Giraudo, E, Bendle, G, Gilham, D, Bicknell, R & Lee, SP 2014, 'Immunotherapy using genetically modified T lymphocytes to target CLEC14A on the tumor vasculature', Cancer Research. https://doi.org/10.1158/1538-7445.AM2014-LB-256

Frumento, G, Zheng, Y, Aubert, G, Raeiszadeh, M, Lansdorp, PM, Moss, P, Lee, S & Chen, FE 2012, 'Cord Blood T Cells Retain Early Differentiation Phenotype Suitable for Immunotherapy After TCR Gene Transfer to Confer EBV Specificity', American Journal of Transplantation, vol. 13, no. 1, pp. 45-55. https://doi.org/10.1111/j.1600-6143.2012.04286.x

Parsonage, G, Machado, LR, Hui, JW, McLarnon, A, Schmaler, T, Balasothy, M, To, KF, Vlantis, AC, van Hasselt, CA, Lo, KW, Wong, WL, Hui, EP, Chan, AT & Lee, S 2012, 'CXCR6 and CCR5 Localize T Lymphocyte Subsets in Nasopharyngeal Carcinoma.', The American Journal of Pathology, vol. 180, no. 3, pp. 1215-22. https://doi.org/10.1016/j.ajpath.2011.11.032

Oldham, K, Parsonage, G, Bhatt, R, Wallace, DM, Deshmukh, N, Chaudhri, S, Adams, D & Lee, S 2011, 'T Lymphocyte Recruitment into Renal Cell Carcinoma Tissue: A Role for Chemokine Receptors CXCR3, CXCR6, CCR5, and CCR6', European urology, vol. 61, no. 2, pp. 385-394. https://doi.org/10.1016/j.eururo.2011.10.035

Dowell, A, Oldham, K, Bhatt, R, Lee, S & Searle, P 2011, 'Long-term proliferation of functional human NK cells, with conversion of CD56(dim) NK cells to a CD56 (bright) phenotype, induced by carcinoma cells co-expressing 4-1BBL and IL-12', Cancer Immunology Immunotherapy. https://doi.org/10.1007/s00262-011-1122-3

Patent

Mussai, F, De Santo, C & Lee, S Dec. 22 2017, CAR-T cell fusion proteins, Patent No. GB1721833.0.

Lee, S & Bicknell, R Sep. 21 2017, Antibodies and related molecules and uses thereof, Patent No. WO/2017/158339 .

Lee, S, Bicknell, R, Sharpe, M & Mount, N Sep. 21 2017, Chimeric antigen receptor, Patent No. WO2017158337.

Lee, S May. 26 2017, T-cell receptor and uses thereof, Patent No. WO/2017/085471, IPC No. C07K 14/725, A61K 38/17.

View all publications in research portal