Banham Group: Haemato-Oncology Group

Monoclonal Antibodies

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.