We have two main areas of interest: understanding the biology of the FOXP family of transcription factors in lymphomas and myeloma in order to develop improved treatment options for patients, and developing novel immunotherapies – in particular therapeutic monoclonal antibodies – for those cancers where there is an unmet need.
Historically, we are experts in the production, characterisation and validation of monoclonal antibodies (mAbs). We are one of the founding members of EuroMabNet, a European network of laboratories involved in the production of mAbs. We have contributed to guidelines for antibody validation, and are also involved in running international workshops to teach young scientists how to approach this effectively.
Novel Immunotherapy Development
We aim to use mAbs to identify new diagnostic and prognostic biomarkers, and as novel cancer therapies. Our most recently developed anti-Jagged1 therapeutic mAbs target the tumour vasculature and inhibit Notch signalling in both solid tumours and haematological malignancies. We are also developing TCR mimic (TCRm) mAbs. These combine the ability of mAbs to bind targets with high affinity and specificity with the ability of T-cell receptors to recognise short peptides derived from intracellular proteins that are presented on the cell surface by major histocompatibility (MHC) class I. This expands the repertoire of antibody targets beyond that of classical cell surface molecules. We are currently evaluating the efficacy and specificity of novel TCRm antibodies against the p53 oncosuppressor.
Transcription Factor Biology
We also study the biology of transcription factors whose expression is clinically relevant in B-cell lymphomas and multiple myeloma. Both B-cell lymphomas and myeloma are tumours derived from B-cells; B-cell lymphomas can reflect different stages of normal B-lymphocyte maturation, whereas myeloma is derived from terminally-differentiated plasma cells. There are many different types of lymphoma that need to be accurately identified in order to provide the most appropriate therapy, and we are especially interested in mature B-cell lymphomas. Diffuse large B-cell lymphoma (DLCBL) is the most common subtype and there is a need to improve currently available therapies as many patients still die of this aggressive disease.
Our group has a particular interest in understanding the role of de-regulated transcription factors in lymphoma, especially the FOXP family of forkhead transcription factors. We have shown that FOXP1 expression is significantly associated with patients’ survival of DLBCL, and can repress antigen presentation in high-risk DLBCL. We are currently using CRISPR/Cas9-mediated genome engineering to silence FOXP1 isoforms in order to further explore the role of FOXP1 in tumour immune surveillance. We are also interested in the role of FOXP2 and whether it has an overlapping or a reciprocal function with FOXP1 in DLBCL and myeloma. Although we primarily study haematological malignancies, we also extend our studies into other types of cancer when this is appropriate.
In addition to the FOXP family, the cancer-testis antigen (CTA) PASD1 is also actively being studied. CTAs represent particularly attractive immunotherapy targets because they are expressed in tumours while their normal tissue expression is restricted to the testis. Our lab identified PASD1 as immunogenic in patients with DLBCL, and we recently demonstrated that it plays a role in regulating the circadian clock. The circadian clock enables living organisms to coordinate the timing of their biology and behaviour with a daily day-night cycle. PASD1 also represents a potential therapeutic target for lymphoma and myeloma.
Dr Michael B Møller and Dr Tina Green, Department of Pathology, Odense University Hospital, Odense, Denmark
Setting International Standards in Antibody Validation
Our group is a founder member of EuroMabNet, the European Network of Monoclonal Antibody Producing Laboratories, and Professor Banham is currently the Vice-President. EuroMabNet is an international network of laboratories, each having an internationally-recognised reputation in the production and use of monoclonal antibodies. Antibodies are valuable tools for scientific research but there is no industry standard for their validation. Many commercial antibodies fail even basic tests of reactivity with their target antigen, while others lack sufficient specificity, leading to wasted time/money and erroneous data in the scientific literature. This is now a topical issue, which has been repeatedly raised within the scientific community. Our group members are involved in the EuroMabNet Antibody Validation Workshops to train young scientists in how to approach antibody validation. We have also made important contributions to the EuroMabNet antibody validation guidelines paper that was published in 2015, and have been actively involved in other activities related to antibody validation standards.
Dr Sally Ashe
Dr Gaynor Bates
Dr Paola Bignone
Mr Simon Brookes
Dr Philip J Brown
Dr Andrew Campbell
Dr Christopher Cooper
Dr Ling Felce
Dr Bridget Fox
Ms Jenny Greig
Ms Hayley Han
Ms Tasneem Hassanali
Ms Rosalind Launchbury
Dr Charles Lawrie
Mr Suketu Patel
Dr John Prime
Dr Stephen Stribbling
Ms Melanie White
Ms Sarah Wiblin
Dr Kah Keng Wong
Ms Jenna Yates
Professor Banham is a STEM Ambassador and a volunteer for Inspiring the Future and is frequently involved with public engagement activities, particularly with a view to encouraging girls to consider a career in science. Other laboratory members also participate in public engagement, including Café Scientifique, school visits, work experience placements and open days for funding agencies and the Oxford Cancer Centre.