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The University of Southampton
Medicine

Professor Christian Ottensmeier MD, PhD, FRCP

Visiting Professor of Experimental Medicine

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Professor Christian Ottensmeier is a Visiting Professor of Experimental Medicine within Medicine at the University of Southampton.

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.

Key academic collaborative links of the group are :
Prf. Freda Stevenson
Prof. Martin Glennie
Prof. Tim Elliott
Prof. Aymen Al-Shamkhani

CIMT and CIP :
Dr. Cedrik Britten, Mainz
Prof. Sjoerd van der Burg, Leiden
Dr. Cecile Gouttefangeas, Tübingen
Dr. Steffen Walter, Immatics, Tübingen

Qualifications

MD Westfälische Wilhelmsuniversität Münster", Germany (1989)
PhD, University of Southampton (1999)

Appointments held

1986-1989 1986-1989 Institute of Pathology of "Von Bodelschwinghsche, Krankenanstalten" Bielefeld, Germany

1989-1991 Department of Medicine (Oncology and Haematology) , Westfälische Wilhelmsuniversität Münster, Germany

1991- 1993 Postdoctoral Research Fellow , Division of Tumour Immunology, Dana-Farber Cancer Institute, Boston, USA

1994 –1999 Senior Registrar in Medical Oncology , Dept of Medical Oncology, University of Southampton, UK

1997 Certificate of Completion of Specialist Training in Medical, Oncology , Conferred by the Medical Royal Colleges, United Kingdom

1995- to date Department of Molecular Immunology/Cancer Sciences Division , University of Southampton, UK

Research interests

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.

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.

Group Members :

Experimental Cancer Medicine Centre Team: Mrs Lindsey Chudley, Dr Ruth Challis, Mr Leon Douglas, Mrs Isla Wheatley Dr Olivier Cexus, Dr Sara Yeates

Supported by Cancer Research UK : Dr. Ann Mander, Dr. Steven Thirdborough, Dr. Katy McCann, Dr. Jana Stasakova

Supported by MRC / DoH : Dr Angelica Cazaly

Department(s)

Cancer Sciences

Affiliate Department(s)

Cancer Sciences Research group

Postgraduate student supervision

Andrew King – 1999 to 2005
Feargal McNicholl –March 2002 to 2005
Preethi Ganesan – Start: 2007
Lindsey Chudley – Start; 2010
Fergus Noble – Start : 2009

Faculty of Medicine

Lead, Experimental Cancer Medicine Centre Southampton

National and International responsibilities

Member CR UK New Agents’ committee
Leukemia and Lymphoma Research Funding committee
Cancer Immunotherapy Collaborative (CIMT) Immunoguiding programme, steering Committee

Development and early phase clinical testing of immunotherapeutics
Using nucleic acids, cellular vaccines and monoclonal antibodies

Development, validation and application of assays for human immune monitoring

Studies of homing and function of human T cells after vaccination

Professor Christian Ottensmeier
Faculty of Medicine, Room AB215, Mailpoint 801, South Academic Block, University Hospital Southampton, Tremona Road, Southampton, SO16 6YD
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