Contact: i.a.mcneish@qmul.ac.uk

Professional interests

Iain McNeish joined the Institute of Cancer in May 2004. He trained in medicine at Oxford and did his PhD at the Institute of Cancer Studies at the University of Birmingham. From 1998 to 2004, he combined training in medical oncology at Hammersmith and Charing Cross Hospitals with post-doctoral research at the Molecular Oncology Unit at Imperial College. The focus of his research is ovarian cancer, which is also his clinical sub-specialisation. His research programme focuses on abnormalities in apoptosis and cell cycle control in ovarian cancer as a target for gene and viral therapy. In particular, his group is studying the therapeutic potential of selectively replicating adenoviral vectors as therapy in ovarian cancer and a phase I trial of one such virus, VTP1 (dl922-947) is due to start in the new Experimental Medicine Unit at Barts in mid-2008. Further, his group is studying the mechanisms by which replicating adenoviral vectors induce cell death and whether this can be augmented with apoptosis inducers, such as chemotherapy or pro-apoptotic genes. His group is also looking at methods of imaging viral activity in whole organisms using bioluminescence, fluorescence and PET imaging.

Most recently, Iain was awarded an MRC programme grant and Senior Clinical Fellowship, worth £1.7 million over 5 years, to continue his research on replicating adenoviruses. In particular, dl922-947 seems to work well in partnership with paclitaxel, a chemotherapy drug commonly used in ovarian cancer, but it is important to understand why, and whether other chemotherapy drugs may also combine well. The programme also seeks to understand how the immune system responds to dl922-947 in the abdominal cavity, where ovarian cancer grows. Finally, the reasons why some ovarian cancer cells do not respond well to dl922-947 will be explored, by studying the patterns of gene expression in sensitive and resistant cells, especially genes that control cell division.

Research Team:

Dr Carin Ingemarsdotter	Postdoctoral research fellow
Dr Michael Salako	Post-doctoral research fellow (joint with Professor F Balkwill)
Dr AM Young	Clinical research fellow
Dr Jermaine Coward	Clinical research fellow (joint with Professor F Balkwill)
Ms Magdalena Flak	PhD student
Ms Claire Connell	PhD student (joint with Dr Sally Wheatley, University of Sussex)
Mr David Leader	Research nurse
Ms Katrina Pirlo	Research assistant
Ms Sarah Williams	Research assistant

Funding:

Medical Research Council, Senior Clinical Fellowship 2007-2012 £1,700,000 "Oncolytic adenoviral gene therapy for ovarian cancer"

Cancer Research UK Clinician Scientist Fellowship 2003-2007 £161,000 p.a. "Dysregulation of apoptotic control in ovarian cancer as a target for gene and viral therapy"

Cancer Research UK Project Grant 2004-2007 £40,000 p.a. "A phase I trial of intravenous VTP1 (dl922-947) in patients with liver metastases from gastrointestinal malignancies"

Cancer Research UK Project Grant 2005-2006 £12,450 "Dysregulation of apoptotic control in ovarian cancer as a target for gene and viral therapy – supplement for PET imaging"

MRC Clinical Training Fellowship (Dr M. Lockley) 2004-2007 £41,480 p.a. "Use of a novel replicating adenovirus, dl922-947, in ovarian carcinoma"

Helene Harris Memorial Trust – Ovarian Cancer Action (co-applicant with Professor F. Balkwill) 2006-2009 £30,000 p.a. "Using adenoviruses to target inflammatory cytokines - gene delivery of biological therapies in ovarian cancer"

Research Advisory Board of the Barts and the London Charitable Foundation, PhD studentship 2006-2009 £68,000 "The mechanisms of activity of the E1A CR2-deleted adenovirus dl922-947 in ovarian cancer"

Cancer Research UK Clinical Centre, Clinical Research Fellowship 2007-2010 £160,000 "The role of the immune system in regulating the activity of oncolytic adenoviral vectors in ovarian cancer"

MRC Experimental Medicine Award (joint applicant with Professor F. Balkwill and Dr N. Avril) 2007-2010 £584,000 "Cytokines in ovarian cancer: a phase II study of CNTO328, an anti-interleukin 6 monoclonal antibody, in women with relapsed ovarian cancer"

Recent Publications:

• Connell C, Wheatley SP, McNeish IA. Nuclear survivin abrogates multiple cell cycle checkpoints and enhances viral oncolysis. Cancer Res 2008;68:7923-31.
• Hagemann T, Lawrence T, McNeish I, Charles KA, Kulbe H, Thompson RG, Robinson SC, Balkwill FR. ‘Re-educating’ tumor-associated macrophages by targeting NF-kB. J Exp Med 2008;205:1261-8.
• Pomel C, Barton DP, McNeish I, Shepherd J. A statement for extensive primary cytoreductive surgery in advanced ovarian cancer. BJOG 2008;115:808-10.
• Baird SK, Aerts JL, Eddaoudi A, Lockley M, Lemoine NR, McNeish IA. Oncolytic adenoviral mutants induce a novel mode of programmed cell death in ovarian cancer. Oncogene 2008;27:3081-90.
• Aiuti A, Bachoud-Lévi A-C, Blesch A, Brenner MK, Cattaneo F, Chiocca EA, Gao G, High KA, Leen AM, Lemoine NR, McNeish IA, Meneguzzi G, Peschanski M, Roncarolo MG, Strayer DS, Tuszynski MH, Waxman DJ, Wilson JM. Progress and prospects: gene therapy clinical trials. Gene Ther 2007;14:1555-63 .
• Hu JC, Coffin RS, Davis CJ, Graham NJ, Groves N, Guest PJ, Harrington KJ, James ND, Love CA, McNeish I, Medley LC, Michael A, Nutting CM, Pandha HS, Shorrock CA, Simpson J, Steiner J, Steven NM, Wright D, Coombes RC.  A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res 2007;12:6737-47.
• Lopes RB, Gangeswaran R, McNeish IA, Wang Y, Lemoine NR. Expression of the IAP protein family is dysregulated in pancreatic cancer cells and is important for resistance to chemotherapy. Int J Cancer 2007;120:2344-52
• Murugaesu N, Schmid P, Dancey G, Agarwal R, Holden L, McNeish I, Savage PM, Newlands ES, Rustin GJ, Seckl MJ. Malignant ovarian germ cell tumors: identification of novel prognostic markers and long-term outcome after multimodality treatment.  J Clin Oncol 2006;24:4862-6.
• Leyton J, Lockley M, Aerts JL, Baird SK, Aboagye EO, Lemoine NR, McNeish IA. Quantifying the activity of adenoviral E1A CR2 deletion mutants using renilla luciferase bioluminescence and 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography imaging. Cancer Res 2006;66:9178-85.
• Martin-Duque P, Quintanilla M, McNeish I, Lopes R, Romero D, Lemoine NR, Vassaux G. Caspase-1 as a radio- and chemo-sensitiser in vitro and in vivo. Int J Mol Med 2006;17:841-7.
• Lockley M, Fernandez M, Wang Y, Li NF, Conroy SE, Lemoine NR, McNeish IA. Activity of the adenoviral E1A deletion mutant dl922-947 in ovarian cancer: comparison with E1A wild-type viruses, bioluminescence monitoring and intraperitoneal delivery in icodextrin. Cancer Res 2006;66:989-98.
• Wheatley S, McNeish IA. Survivin: a protein with dual roles in mitosis and apoptosis. Int Rev Cytol 2005;247:35-88.
• McNeish IA, Lopes R, Bell SJ, McKay TR, Fernandez M, Lockley M, Wheatley SP, Lemoine NR. Survivin interacts with Smac/DIABLO and is downregulated, but is redundant in Smac-mediated apoptosis. Exp Cell Res 2005;302:69-82.
• McNeish IA, Kanfer EJ, Haynes R, Giles C, Harland SJ, Rustin GJR, Newlands ES, Seckl MJ. Paclitaxel-containing high dose chemotherapy for relapsed or refractory testicular germ cell tumours. Brit. J Cancer 2004;90:1169-75.
• Lemoine NR, McNeish IA. Gene transfer: Bax to the future for cancer therapy? Gut 2004;53:478-9.
• McNeish IA, Bell SJ, Lemoine NR. Progress and Prospects: Cancer gene therapy using tumour suppressor genes. Gene Ther 2004;11:497-503.
• Pardo OE, Lesay A, Arcaro A, Lopes R, Ng BL, Warne PH, McNeish IA, Tetley TD, Lemoine NR, Mehmet H, Seckl MJ, Downward J. FGF-2-mediated translational control of IAPs blocks mitochondrial release of Smac/DIABLO and apoptosis in Small Cell Lung Cancer cells. Mol Cell Biol 2003;23:7600-10.
• McKay TR, Bell S, Tenev T, Stoll V, Lopes R, Lemoine NR, McNeish IA. Pro-caspase-3 expression in ovarian carcinoma cells increases survivin transcription which can be countered with a dominant negative mutant, survivin T34A; a combination gene therapy strategy. Oncogene 2003;22:3539-47.
• McNeish IA, Bell S, McKay T, Tenev T, Marani M, Lemoine NR. Expression of Smac/DIABLO in ovarian carcinoma cells induces apoptosis via a caspase-9-mediated pathway. Exp Cell Res 2003;286:186-198.
• Green NK, McNeish IA, Doshi R, Searle PF, Kerr DJ, Young LS. Immune enhancement of nitroreductase-induced cytotoxicity: studies using a bicistronic adenovirus vector. Int J Cancer 2003;104:104-12.
• McNeish IA, Strickland S, Holden L, Rustin GJR, Foskett M, Seckl M, Newlands ES. Low-risk persistent gestational trophoblastic disease: outcome following initial treatment with low-dose methotrexate and folinic acid, 1992 – 2000 J Clin Oncol 2002;20:1838-44.
• McNeish IA, Tenev T, Bell S, Marani M, Vassaux G, Lemoine N. Herpes simplex virus thymidine kinase/ganciclovir-mediated cell death is enhanced by co-expression of caspase-3 in ovarian carcinoma cells. Cancer Gene Ther 2001;4:308-19.
• Tenev T, Marani, M, McNeish I, Lemoine NR. Pro-caspase-3 overexpression sensitises ovarian cancer cells to proteasome inhibitors. Cell Death Diff 2001;8:256-64.

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