Dr Steven Lee is a Senior Research Fellow whose research is focused on engineering T cells to target human tumours, either by attacking the malignant cells directly, or targeting the blood vessels that supply the tumour.
Senior Research Fellow, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham.
Background and Research focus
Steve’s research group is investigating ways to engineer T cells using either chimeric antigen receptors (CARs) or T cell receptors (TCRs) to target the tumour cell or vital stromal components. In particular, his current work is exploring the use of CARs to target antigens selectively expressed on the tumour vasculature in order to compromise blood flow in tumour tissue and thereby provide therapeutic benefit (work in collaboration with Prof Roy Bicknell). One such marker, CLEC14A, is highly expressed on the vasculature of a wide range of common human cancers but is poorly expressed in the vasculature of healthy tissue. CARs targeting this marker have generated exciting results both in vitro and in vivo and he is currently liaising closely with the Cell and Gene Therapy Catapult in preclinical development of this strategy leading towards a phase I clinical trial. In addition his group is using T cell receptor gene transfer approaches to target virally encoded antigens for Epstein-Barr virus-associated malignancies such as Nasopharyngeal carcinoma, Hodgkin’s Lymphoma NK-T lymphomas and Post-transplant Lymphoproliferative Disease.
Steve received a Career Development Award from the MRC, then a Senior Cancer Research Fellowship from Cancer Research UK, and continues to receive funding from this and other organisations including the Wellcome Trust. Steve’s lab has extensive experience in T cell cloning and assays of T cell function, as well as use of recombinant viruses for genetic engineering of immune cells. His group aims to use these approaches to develop safe and effective T cell-based therapies for human cancer. As part of this work he collaborates with many colleagues within the CIIC as well as others in the UK, Europe, Hong Kong and the USA.
T lymphocytes; tumour immunology; tumour immunotherapy; T cell trafficking; adoptive T cell therapy; CAR and TCR engineering; Epstein-Barr virus (EBV); EBV-associated malignancies.
Dr Lee is an enthusiastic communicator on the theme of immune-based therapies for cancer presenting his work to both academics and the general public. In addition to his research commitments, Dr Lee makes substantial contributions to teaching undergraduate, postgraduate and medical students. In particular, he is the lead coordinator for the Immunotherapy Small group teaching sessions on the MBChB course as well as delivering lectures on the MBChB, BMedSci and MRes Cancer Sciences programmes at the University of Birmingham. Dr Lee also serves as Radiation Protection Supervisor for the Institute and Training Lead for the Birmingham CRUK Cancer Centre.
Knoblich K, Migoni SC, Siew SM, Jinks E, Kaul B, Jeffery HC, Baker A, Suliman M, Vrzalikova K, Mehanna H, Murray PG, Barone F, Newsome PN, Hirschfield G, Kelly D, Oo Y, Lee SP, Parekkadan B, Turley SJ, Fletcher AL. The human lymph node microenvironment unilaterally regulates T cell activation and differentiation PLoS Pathogens 2018 (in press)
Tubb V, Schrikkema DS, Croft NP, Purcell AW, Linnemann C, Freriks MR, Chen F, Long HM, Lee SP, Bendle GM. Isolation of T cell receptors targeting recurrent neoantigens in hematological malignancies. Journal for ImmunoTherapy of Cancer 2018 (in press)
Zheng Y, Parsonage G, Zhuang X, Machado LR, James CH, Salman A, Searle PF, Hui EP, Chan ATC and Lee SP. Human Leukocyte Antigen (HLA) A*1101-restricted Epstein-Barr virus-specific T-cell receptor gene transfer to target Nasopharyngeal carcinoma. Cancer Immunol Res 2015 3(10):1138-47
Frumento G, Zheng Y, Aubert G, Raeiszadeh M, Lansdorp PM, Moss P, Lee SP, Chen FE. Cord blood T cells retain early differentiation phenotype suitable for immunotherapy after TCR gene transfer to confer EBV specificity. Am J Transplant. 2013 Jan;13(1):45-55
Oldham KA, Parsonage G, Bhatt RI, Wallace DMA, Deshmukh N, Chaudhri S, Adams DH and Lee SP. T lymphocyte recruitment into Renal Cell Carcinoma tissue: A role for chemokine receptors CXCR3, CXCR6, CCR5 and CCR6. Eur Urol. 2012 61, 385-394.
Parsonage G, Machado LR, Hui J, McLarnon A, Schmaler T, Balasothy M, To K-F, Vlantis AC, van Hasselt CA, Lo KW, Wong W-L, Hui EP, Chan A and Lee SP. CXCR6 and CCR5 localise T lymphocyte subsets in Nasopharyngeal Carcinoma. Am J Pathol. 2012 180, 1215-22.
Fox CP, Haigh TA, Taylor GS, Long HM, Lee SP, Shannon-Lowe C, O’Connor S, Bollard CM, Iqbal J, Chan WC, Rickinson AB, Bell AI, Rowe M. A novel latent membrane 2 transcript expressed in Epstein-Barr virus-positive NK and T cell lymphoproliferative disease encodes a target for cellular immunotherapy. Blood. 2010 116, 3695-3704.
Brooks, JM, Lee SP, Leese AM, Thomas WA, Rowe M and Rickinson AB. Cyclical Expression of EBV Latent Membrane Protein 1 in EBV-Transformed B Cells Underpins Heterogeneity of Epitope Presentation and CD8+ T Cell Recognition. J Immunol. 2009 182, 1919–1928.
Machado, L, Jarrett R, Morgan S, Murray P, Hunter B, Crocker J, Thomas W, Steven N, Ismail T, Chapman A, Adams D, Lee S. Expression and function of T cell homing molecules in Hodgkin’s Lymphoma. Cancer Immunol. Immunother. 2009 58, 85-94.
Long HM, Haigh TA, Gudgeon NH, Leen AM, Tsang CW, Brooks J, Landais E, Houssaint E, Lee SP, Rickinson AB, Taylor GS. CD4+ T-cell responses to Epstein-Barr virus (EBV) latent-cycle antigens and the recognition of EBV-transformed lymphoblastoid cell lines. J Virol. 2005 Apr;79(8):4896-907
Lee SP, Brooks JM, Al Jarrah H, Thomas WA, Haigh TA, Taylor GS, Humme S, Schepers A, Hammerschmidt W, Yates JL, Rickinson AB and Blake NW. CD8 T cell recognition of endogenously expressed Epstein Barr virus nuclear antigen 1. J.Exp.Med. 2004 199, 1409-1420
Chapman ALN, Rickinson AB, Thomas WA, Jarrett RF, Crocker J and Lee SP. Epstein-Barr Virus-Specific Cytotoxic T Lymphocyte Responses in the blood and tumour site of Hodgkin’s Disease patients: Implications for a T Cell-Based Therapy. Cancer Research. 2001 61: 6219-6226.