Dr Neil Steven

Neil Steven_cropresize1

Neil Steven is a consultant oncologist with a  strong interest in immunotherapy clinical trials, particularly  in skin cancer, including both melanoma and also rarer forms of cutaneous malignancy such as Merkel Cell Carcinoma.
Position:

Senior Lecturer, School of Cancer Sciences, University of Birmingham

Honorary Consultant in Medical Oncology, University Hospitals Birmingham

Deputy Clinical Director of CRCTU, leading Early Phase Adult Solid Tumour Trials

Email: n.m.steven@bham.ac.uk

LinkedIn profile

Background and Research focus

Neil is a medical oncologist with a strong focus on developing immunotherapy for solid tumours, and in virus-associated malignancies. Following clinical training in medical oncology, Neil carried out a PhD in Professor Alan Rickinson’s group at Birmingham, his research focussing on the T cell response to Epstein Barr Virus (EBV). A major current focus is on early phase clinical trials, and Neil is Deputy Clinical Director of the Cancer Research UK Clinical Trials Unit, with a responsibility for leading early phase trials in adult solid tumours. As such he has close involvement with a large number of clinical trials in solid tumours, several including novel/emerging immunotherapy agents, some academic-driven, and some involving industry collaborations.

Neil has specialized clinically in colorectal cancer and more recently, on skin cancer, where he is the medical oncology lead within the skin cancer multi-disciplinary team, a key focus being melanoma. His laboratory studies in this area centre on understanding the nature the tumour microenvironment and how this differs between patients, with a view to improving and targeting emerging immunotherapy strategies. These include checkpoint blockade, which has shown substantial promise in melanoma, and Neil has a number of collaborations with pharmaceutical companies in this area.

In addition, Neil has retained a major interest in virus-associated cancers, and has played a leading role alongside Dr Graham Taylor in establishing a vaccine programme for EBV-associated tumours, in particular Nasopharyngeal Carcinoma. This represents the culmination of years of fundamental research on EBV immunology to the clinic, and following a successful Phase I trial, a Phase II trial is currently ongoing in the UK and Asia. A developing area of interest is in Merkel Cell Carcinoma (MCC), a rare skin cancer associated with poor prognosis, recently found to be caused by a newly discovered tumour virus. Notably, Neil is Chief Investigator of a clinical trial testing the tyrosine kinase inhibitor Pazopanib on advanced Merkel Cell Carcinoma patients. In addition, a key aim is to understanding the immune response to Merkel Cell Virus in MCC patients, as well as nature of the tumour microenvironment in these rare tumours, with a view to developing novel immunotherapeutic strategies. immunosurveillance of cellular stress. 

Expertise

Early phase clinical trials; solid tumours;  immunotherapy; melanoma; Merkel Cell Carcinoma; colorectal cancer; virus-associated malignancies; checkpoint blockade.

Other activities

In addition to leading his own research group, Neil is closely involved in management of the Wellcome Trust Clinical Research Facility, and also is active in fundraising for skin cancer-related research. Neil also serves a lead advisor on clinical trials for the CIIC grouping.

Publications

Angevin E, Tabernero J, Elez ME, Cohen SJ, Bahleda R, Van Laethem JL, Ottensmeier CH, Lopez-Martin JA, Clive S, Joly F, Ray-Coquard I, Dirix LY, Machiels JP, Steven NM, Reddy M, Hall B, Puchalski TA, Bandekar R, van de Velde H, Tromp B, Vermeulen J, Kurzrock R. A phase 1/2, multiple-dose, dose-escalation study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2014 Feb 21.

Wheat R, Roberts C, Waterboer T, Steele J, Marsden M, Steven N, Blackbourn D. Inflammatory cell distribution in primary Merkel cell carcinoma. Cancers 2014, 6(2), 1047-1064; doi:10.3390/cancers6021047

Hui EP, Taylor GS, Jia H, Ma BB, Chan SL, Ho R, Wong WL, Wilson S, Johnson BF, Edwards C, Stocken DD, Rickinson AB, Steven NM, Chan AT. Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients. Cancer Res. 2013 Mar 15;73(6):1676-88.

Simpson AA, Mohammed F, Salim M, Tranter A, Rickinson AB, Stauss HJ, Moss PA, Steven NM, Willcox BE. Structural and energetic evidence for highly peptide-specific tumor antigen targeting via allo-MHC restriction. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21176-81.

Steele JC, Rao A, Marsden JR, Armstrong CJ, Berhane S, Billingham LJ, Graham N, Roberts C, Ryan G, Uppal H, Walker C, Young LS, Steven NM. Phase I/II trial of a dendritic cell vaccine transfected with DNA encoding melan A and gp100 for patients with metastatic melanoma. Gene Ther. 2011 Jun;18(6):584-93.

Rees L, Tizard EJ, Morgan AJ, Cubitt WD, Finerty S, Oyewole-Eletu TA, Owen K, Royed C, Stevens SJ, Shroff RC, Tanday MK, Wilson AD, Middeldorp JM, Amlot PL, Steven NM. A phase I trial of epstein-barr virus gp350 vaccine for children with chronic kidney disease awaiting transplantation. Transplantation. 2009 Oct 27;88(8):1025-9.

Palmer DH, Midgley RS, Mirza N, Torr EE, Ahmed F, Steele JC, Steven NM, Kerr DJ, Young LS, Adams DH. A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma. Hepatology. 2009 Jan;49(1):124-32.

Taylor GS, Haigh TA, Gudgeon NH, Phelps RJ, Lee SP, Steven NM, Rickinson AB. Dual stimulation of Epstein-Barr Virus (EBV)-specific CD4+- and CD8+-T-cell responses by a chimeric antigen construct: potential therapeutic vaccine for EBV-positive nasopharyngeal carcinoma. J Virol. 2004 Jan;78(2):768-78.

Steven NM, Annels NE, Kumar A, Leese AM, Kurilla MG, Rickinson AB. Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response. J Exp Med. 1997 May 5;185(9):1605-17.

Steven NM, Leese AM, Annels NE, Lee SP, Rickinson AB. Epitope focusing in the primary cytotoxic T cell response to Epstein-Barr virus and its relationship to T cell memory. J Exp Med. 1996 Nov 1;184(5):1801-13.

Rickinson AB, Lee SP, Steven NM. Cytotoxic T lymphocyte responses to Epstein-Barr virus. Curr Opin Immunol. 1996 Aug;8(4):492-7.