Professor Iain McNeish
Research Interests
Professor Iain Mcneish's main research theme are in Cancer Genetics, Cancer Gene Therapy, Cancer Immunology, Clinical Trials, Ovarian Cancer, Virotherapy and Oncolytic Viruses.
My lab focuses on developing novel therapies for ovarian cancer. Each year, nearly 7,000 women in the UK are diagnosed with ovarian cancer and at least two-thirds of them will die from their disease, a proportion that has not improved greatly in the past 15 years. There is a great need to develop new therapies for this disease, based upon greater understanding of its biology.
Research in the lab concentrates on the use of oncolytic adenoviruses as a potential new treatment for ovarian cancer. These viruses infect cancer cells, replicate selectively within them, killing them, and then exit to infect neighbouring cells. We have previously shown that the second generation adenovirus mutant dl922-947 has considerable activity in ovarian cancer. Oncolytic adenoviruses deregulate multiple cell cycle checkpoints to promote virus replication and kill cancer cells by a unique non-apoptotic mechanism. Most recently, we have identified potential predictive biomarkers of adenovirus activity in ovarian cancer and have shown that adenoviruses induce widespread genomic DNA damage in cancer cells, activating ATR-Chk1. Moreover, inhibition of Chk1 increases virus activity in resistant cells. We are currently exploring the link between cellular DNA damage repair and adenovirus biology, especially the role of Homologous Recombination repair – new results suggest that 50% of high grade serous ovarian cancers have defective Homologous Recombination.
In addition, we are investigating how the unique immunological environment of the peritoneal cavity in ovarian cancer influences virus biology. Adenoviruses induce acute inflammatory responses rapidly after infection. We have shown recently that these responses act to reduce virus-induced death and that inhibition of Tumour Necrosis Factor-α can augment adenovirus activity in ovarian cancer. We have also shown that the spleen is the site of earliest host infection and may be the source of many acute cytokines released following infection and we are now investigating the specific role of splenic and peritoneal macrophages in the acute inflammatory response.
Finally, Michelle Lockley and I are responsible for all the non-surgical treatment of women with ovarian cancer at St Bartholomew's Hospital and run a series of early and late phase clinical trials for women at all stages of the disease, through which patients gain access to novel agents.
Profile
- 1992 – Qualified in Medicine (University of Oxford)
- 1995 – MRCP
- 1998 – PhD (University of Birmingham)
- 1999 – ICRF Clinician Scientist Fellowship, Imperial College London
- 2003 – Completed training in Medical Oncology
- 2003 – Cancer Research UK Clinician Scientist
- 2004 – Senior Lecturer in Medical Oncology, Barts Cancer Institute, Honorary Consultant in Medical Oncology Barts and the London NHS Trust
- 2007 – MRC Senior Clinical Fellow
- 2008 – Professor of Gynaecological Oncology, Barts Cancer Institute.
Funding
- June 2005: Ovarian Cancer Action project grant (co-applicant with Prof. F. Balkwill), Cytokines in ovarian cancer: £150,000
- January 2006: Association for International Cancer Research project grant (AICR) (co-applicant with Dr J. Wilson and Prof. F. Balkwill) Targeting CXCR4 and its ligand in ovarian cancer: £200,000
- March 2006: MRC Experimental Medicine Award (co-applicant with Prof. F. Balkwill and Dr N. Avril). A phase II study of CNTO328, a monoclonal anti-IL6 antibody, in women with relapsed ovarian cancer: £584,000
- April 2006: St Bartholomew's & the Royal London Charitable Foundation PhD studentship. Oncolytic virus therapy for ovarian cancer: the mechanisms of activity of the E1A-CR2-deleted adenovirus dl922-947: £90,000
- July 2007: Barts Cancer Research UK Clinical Centre Clinical Research Fellowship. Immunocompetent models of adenovirus gene therapy for ovarian cancer: £245,000
- May 2007: MRC Senior Clinical Fellowship. Oncolytic adenoviral gene therapy for ovarian cancer: £1,700,000
- October 2008: DoH NIHR Capital Equipment Award: £484,362
- March 2009: Barts and the London Charity Cancer Fund, Consumables awards: £14,800
- July 2009: Cancer Research UK CTAAC (Clinical Trials Awards and Advisory Committee) and Astra Zeneca. SaPPROC – Saracatininb and weekly paclitaxel in platinum-resistant ovarian cancer: £193,278
- December 2009: Cancer Research UK CTAAC (co-applicant). ICON8 - an international two-stage randomised trial of dose-fractionated chemotherapy compared to standard three-weekly chemotherapy, following immediate primary surgery or as part of delayed primary surgery, for women with newly diagnosed epithelial ovarian cancer: £686,631
- January 2011: Barts Cancer Research UK Centre Clinical Research Fellowship. The role of DNA damage and repair pathways in the efficacy of oncolytic adenoviruses in ovarian cancer: £227,000
Key Publications
Oncolytic adenoviral mutants induce a novel mode of programmed cell death in ovarian cancer. Baird S.K., Aerts J.L., Eddaoudi A., Lockley M., Lemoine N.R., McNeish I.A. Oncogene (2008) 27: 3081-3090. PMID: 18071311
Nuclear survivin abrogates multiple cell cycle checkpoints and enhances viral oncolysis. Connell C., Wheatley S.P., McNeish I.A. Cancer Res. (2008) 68: 7923-7931. PMID: 18829549
Genomic DNA damage and ATR-Chk1 signaling determine oncolytic adenoviral efficacy in human ovarian cancer cells.Connell CM, Shibata A, Tookman LA, Archibald KM, Flak MB, Pirlo KJ, Lockley M, Wheatley SP, McNeish IA. J Clin Invest. 2011 Mar 7. pii: 43976. doi: 10.1172/JCI43976. [Epub ahead of print] PMID: 2138350
Low-dose paclitaxel synergizes with oncolytic adenoviruses via mitotic slippage and apoptosis in ovarian cancer. Ingemarsdotter C.K., Baird S.K., Connell C.M., Oberg D., Hallden G., McNeish I.A. Oncogene. 2010 Nov 11;29(45):6051-63. PMID: 2072992
Further Publications
For additional publications, please click here.
Research Group
- Carin Ingemarsdotter (Postdoctoral Research Assistant)
- Darren Ennis (Tissue Collection Officer)
- Laura Tookman (Clinical Research Fellow)
- Michelle Lockley (Clinical Senior Lecturer)
External Activities
- Member, Cancer Research UK CTAAC International Advisory Panel, 2007 –
- Member, Breakthrough Breast Cancer Intramural Research Committee, 2008 –
- Member, Association for International Cancer Research Science Advisory Board, 2010 -
- Member, Cancer Research UK CIRB (Central Institutional Review Board), 2006 –
- Member NCRI Gynaecological Cancer Clinical Studies Group, 2006 –
- Chair, NCRI Gynaecological Cancer CSG Ovarian subgroup, 2008 –
- Member, Scottish Gynaecological Cancer Clinical Trials Group, 2006 –
- Member, GCIG (Gynecologic Cancer Intergroup), 2008 –
- Editorial Board Member, 'Gene Therapy', 2008 –
