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Associate Professor, Faculty of Medicine & Health Sciences
Main Research Area:
The use of autoantibodies in the early detection of cancer:
Early detection of cancer, at a stage when the tumour is still localised and treatable, is the goal of any screening tool and new approaches are required which do not rely on already circulating tumour cells, or disease bulk.
Cancer cells often present a number of novel, aberrantly expressed or mutated proteins, or even abnormally large amounts of normal proteins. The immune system is uniquely adapted to detect such changes and even small quantities of such proteins can lead to the production of a specific immune response in the form of specific autoantibodies. A very small tumour bulk, that could not be measured using conventional tumour marker assays, could therefore be identified following measurement of such antibodies. Due to the heterogeneous nature of most solid tumours the measurement of autoantibodies to only one cancer associated antigen is unlikely to be sufficiently sensitive to make this approach useful as a screening test. Whereas measurement of autoantibodies to a panel of such antigens, if correctly managed, could provide a simple tool that is both sensitive and specific. Autoantibodies to cancer antigens have been shown to be detectable in a number of different solid tumours. In some cases these autoantibodies have also been identified 4-5 years before the cancer could be diagnosed using more routine methodologies (eg mammography for breast cancer and CT for lung cancer). Our group has published data that demonstrate the presence of tumour associated autoantibodies in a number of solid cancers. We have recently reported that approximately 40% of all lung cancers (and 52% of small cell lung cancers - SCLC's) can be detected by measuring autoantibodies to a range of E.coli expressed and purified tumour associated antigens (TAAs), when compared to an age, gender and smoking matched group of 'normal' individuals (with a 90% specificity). Work is ongoing to try to identify a different panel of antigens which will be useful in the earlier detection of other solid tumours like breast, colorectal and hepatocellular carcinomas. It will also be interesting to determine whether measurement of such antibodies following surgical resection and treatment, may also provide prognostic information for the clinician. Correlation of the antibody results with tissue expression of the genes of interest is also ongoing (where possible). Expression of truncated proteins, as well as TAAs in a range of expression systems including Baculovirus, yeast and mammalian systems is also ongoing to identify immunogenic regions and the importance of expression systems in their production.
Phage display and expression of immunoglobulins.
Nature of the immune response in autoimmune diseases.
Immunoglobulin gene usage in B-cell malignancies.
Leishmaniasis.
Analysis of tumour-assocaited antibodies in a range of solid tumours.
Expression of antigens in a range of expression systems.
T-cell responses to TAAs.
Identification of novel TAAs.
D Floor, East BlockQueen's Medical Centre Nottingham, NG7 2UH
telephone: +44 (0) 115 823 0695 fax: +44 (0) 115 823 0704 email: scs-enquiries@nottingham.ac.uk