个人简介
Christian Ottensmeier is Professor in Experimental Cancer Medicine. He graduated in Münster, Germany and began his specialist training there. After a 3 year training fellowship in the Dana Farber Cancer Institute in Boston, Massachusetts, he moved to Southampton. He completed his oncology training and also undertook his PhD here. He has been a consultant in medical oncology since 2000.
Clinically his interests are thoracic malignancies and melanoma, and he has co-developed a number of national NCRI studies in lung cancer. He manages a broad and active clinical trials portfolio in both lung cancer and melanoma.
Christian leads the Experimental Cancer Medicine Centre in Southampton (http://www.ecmcnetwork.org.uk/) and the early translation of immunotherapeutic strategies into the clinic is his core academic interest. The portfolio of his own trials includes single centre and multicentre studies with both immunotherapeutics developed in house as well as collaborative work with industry. Together with Dr. Katy Rezvani at the Hammersmith Hospital he was successful in obtaining the first cancer trial grant in the UK from the Efficacy and Mechanisms Evaluation board (http://www.eme.ac.uk/) of the National Institute for Health Research in the UK for a vaccine study in haematological malignancies. A parallel strand of investigation examines the effect of chemo-immunotherapy on both anticancer as well as bystander immunity in small cell lung cancer with an anti-CTLA4 antibody. This multicenter study recruits collaboratively with the Barts (Dr. Peter Slozarek), Cambridge (Prof. Tim Eisen), Leeds (Dr. Clive Mulatero) and Sheffield (Dr. Sarah Danson) ECMCs as well as with Poole (Dr. Tom Geldart) and Brighton (Prof. Michael Schmidt).
Christian also contributes to early phase industry sponsored immunotherapy studies, utilizing a wide range of strategies including viral and cellular delivery strategies.
He has served on a number of industry advisory boards and DSMBs for industry led studies and is also a member of the Clinical Development partnership between Cancer Research UK and Astra Zeneca (http://www.clinicalpartnerships.com/team/sab).
He is a member of a number of national peer reviewed funding committees for Cancer Research UK (http://science.cancerresearchuk.org/) and Leukemia and Lymphoma Research (http://beatbloodcancers.org/research).
The overarching aim of his laboratory group is the preclinical development and early phase clinical testing of strategies to induce anti-tumour immune responses in patients. (After an initial focus on B cell malignancies the majority of the work is now in solid tumours. This has led to three linked but distinct areas of investigation: Detailed immunological evaluation of the effect of immunological intervention in patients, assay development and validation, and finally mechanistic studies in murine models as well as human modelling of immune responses to vaccination for further preclinical cancer vaccine development. The aim is to complete the loop back into the clinic.
Christian holds programmatic funding from Leukemia and Lymphoma Research and Cancer Research UK.
研究领域
Translational Immunotherapy Group
The Translational Immunotherapy Group is headed by Christian Ottensmeier, Professor in Experimental Cancer Medicine, and CRUK Senior Clinical Research Fellow.
The overarching aims of the group are the preclinical development and early phase clinical testing of strategies to induce anti-tumour immune responses in patients with B cell malignancies and solid tumours. This has led to a number of parallel strands of investigation:
Early Phase Clinical Testing
Our research programme has developed out of a special interest in the immunogenetics of B-cell lymphoma. Working closely with the Genetic Vaccines Group (Prof. Freda Stevenson), designs for individual DNA fusion vaccines targeting the patient-specific malignant B-cells have been successfully translated into the clinic. Phase I/II testing is complete in patients with follicular lymphoma, and ongoing in patients with multiple myeloma. Professor Ottensmeier is also Principal Investigator of ongoing multi-centre clinical trials to test DNA fusion vaccines targeting solid tumours. The CRUK-sponsored anti-CEA DNA vaccination (ACVA) study for CEA-expressing cancers is currently recruiting patients from Southampton, Leeds, Edinburgh and Portsmouth, and the anti-Prostate Specific Membrane Antigen (PSMA) DNA vaccination study has just completed recruitment in collaboration with the Royal Marsden Hospital. This phase I/II study in prostate cancer is the first human study that also tests a novel physical delivery strategy to improve the efficiency of DNA vaccine delivery in humans (electroporation). This work is undertaken in close collaboration with Inovio.
Assay Development and Validation
As part of the Translational Clinical Research Group, the group has invested major efforts into the development, methodical evaluation and validation of robust endpoint assays to provide the immunological tools for assessing the outcome of clinical testing within the stringent regulatory framework in UK and Europe. This has been enhanced by collaborations with the European Cancer Immunotherapy (CIMT) consortium, consisting of more than 20 academic centres throughout Europe. We are co-organisers of a European-wide interlaboratory testing initiative to assess the performance and reliability of cellular assays (tetramer staining, ELISPOT, ICS). A key aim is to develop assays to a high standard for inter-study comparablility and transparent assay reporting (www.miataproject.org)
Mechanistic Studies
Further complementary studies are being undertaken with the aim of increasing our understanding of the mechanisms underlying tumour immunology, thereby informing the rational design of new therapeutic approaches to cancer. In close collaboration with Dr Tony Williams (LINK), we are using FACS based methodologies to examine the relationship between tissue-specific Tumour Infiltrating Lympocytes (TILs) and inhibitory regulatory T cells (Tregs) in colorectal cancer. Multicolour FACS analysis of B, CD4+,CD8+ T cells and NK cells is also being used to evaluate the effect of systemic therapies on the immune system of patients with lung cancer and thymoma.
Preclinical Vaccine Development
Other strategies to enhance the immunological effectiveness of the vaccines are also being investigated and include the pre-clinical design and modelling and testing of novel DNA vaccines with different immunoenhancing adjuvants. The aim is to use these strategies for the next round of clinical testing.
近期论文
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Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis - Mellone, Massimiliano, Hanley, Christopher, Thirdborough, Stephen, Mellows, Toby, Garcia, Edwin, Woo, Jeongmin, Tod, Joanne, Frampton, Steven, Jenei, Veronika, Moutasim, Karwan, Kabir, Tasnuva D., Brennan, Peter A, Venturi, Giulia, Ford, Kirsty, Herranz, Nicolas, Lim, Kue Peng, Clarke, James, Lambert, Daniel W., Prime, Stephen S., Underwood, Timothy J., Vijayanand, Pandurangan, Eliceiri, Kevin W., Woelk, Christopher, King, Emma, Gil, Jesus, Ottensmeier, Christian and Thomas, Gareth Published:2016Publication:AgingPage Range:1-19doi:10.18632/aging.101127PMID:27992856
Human papillomavirus drives tumor development throughout the head and neck: improved prognosis is associated with an immune response largely restricted to the oropharynx - Chakravarthy, Ankur, Henderson, Stephen, Thirdborough, Stephen M., Ottensmeier, Christian H., Su, Xiaoping, Lechner, Matt, Feber, Andrew, Thomas, Gareth J. and Fenton, Tim R. Published:2016Publication:Journal of Clinical OncologyPage Range:1-12doi:10.1200/JCO.2016.68.2955
Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors - Wood, Oliver, Woo, Jeongmin, Seumois, Gregory, Savelyeva, Natalia, Mccann, Katy J., Singh, Divya, Jones, Terry, Peel, Lailah, Breen, Michael S, Ward, Matthew, Garrido Martin, Eva, Sanchez-Elsner, Tilman, Thomas, Gareth, Vijayanand, Pandurangan, Woelk, Christopher H., King, Emma and Ottensmeier, Christian Published:2016Publication:OncotargetPage Range:1-17doi:10.18632/oncotarget.10788PMID:27462861
Outcome and biomarker analysis from a multi-centre phase 2 study of ipilimumab in combination with carboplatin and etoposide (ICE) as first line therapy for extensive stage small cell lung cancer - Arriola, E., Wheater, M., Galea, I., Cross, N., Maishman, T., Hamid, D., Stanton, L., Cave, J., Geldart, T., Mulatero, C., Potter, V., Dansen, S., Woll, P.J., Griffiths, R., Nolan, L. and Ottensmeier, C. Published:2016Publication:Journal of Thoracic OncologyPage Range:1-27doi:10.1016/j.jtho.2016.05.028PMID:27296105
Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma - Noble, Fergus, Mellows, Toby, McCormick Matthews, Leo H., Bateman, Adrian, Harris, Scott, Underwood, Tim, Byrne, James P., Bailey, Ian S., Sharland, Donna M., Kelly, Jamie J., Primrose, John N., Sahota, Surinder S., Bateman, Andrew R., Thomas, Gareth J and Ottensmeier, Christian H. Published:2016Publication:Cancer Immunology ImmunotherapyVolume:65, (6)Page Range:651-662doi:10.1007/s00262-016-1826-5PMID:27020682
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