About
Our key strength is the interdisciplinary nature of the work we undertake, from basic cellular and molecular biology, to the epidemiology of service provision. We also have particular strengths in basic and translational immunology, and tumour survival in lymphoma and solid tumours.
We incorporate the Southampton Cancer Research UK Centre, and our research involves significant collaboration between:
- laboratory-based cancer researchers
- clinicians specialising in treating cancer patients
- research teams with expertise in fields such as medicinal chemistry and biophysical sciences
Immunotherapeutic antibodies and vaccines
We have contributed significantly to the development of new cancer immunotherapy treatments by building on a deep understanding of antibody effector functions, particularly mediated via Fc receptors, and the immunobiology of cytotoxic T cells.
We're continuing to define DNA cancer vaccines for targeted therapy and have completed 5 Phase I/II trials in lymphoma, multiple myeloma and solid cancers since 2008.
We are also developing Good Clinical Laboratory Practice (GCLP) level human immunometry. We have extended our capability to full cell-mediated immune profiling at the functional level and exome-based next-generation sequencing (NGS). This is thanks to the CRUK/DH-funded Experimental Centre for Cancer Medicine and our new 400m2 GCLP laboratory in the SCBR.
Molecular and cellular immunology
Development of new T cell-based immunotherapies in cancer is supported by our deep understanding of the mechanisms of antigen processing and presentation, co-stimulation, and the role of the tumour microenvironment in shaping its growth.
We are investigating the molecular mechanism of peptide antigen selection in antigen presentation, and how polymorphic variation in the enzymes that generate antigenic peptides influences immune responsiveness.
Tumour immunological environment
We are investigating the function of the myofibroblast-rich stroma of head and neck and lung cancers, in supressing anti-tumour T cell responses in cancer patients. This work focusses on improving immunotherapy in the context of stromal immunosuppression, and has led to a new programme aimed at predicting cancer patients’ responsiveness to immunotherapy and vaccination based on genomic and epigenomic profiling of tumour, stroma, and infiltrating immunocytes at single-cell resolution.
Leukaemia and Lymphoma Research Centre of Excellence for Research on Chronic Lymphocytic Leukaemia (CLL)
This work integrates with the UK national CLL strategy, via the UK CLL Trials Biobank. It exploits strong collaboration with:
Key achievements
- We have elucidated the effector mechanism of the FDA-approved anti-CD20 therapeutic mAb, ofatumumab and experimental therapeutic obinutuzumab, and demonstrated that FcgRIIb expression on tumour targets is a strong negative prognostic factor for anti-CD20 treatment.
- Our research linking the IGHV mutational status to B-cell receptor signalling in lymphoid malignancies has led to identification of follicular B cell lymphoma endotypes, allowing stratified approaches to therapy.
- We have identified somatic alterations driving CLL, and novel methods for inducing selective apoptosis in CLL cells.
- We have discovered a new CtBP regulatory mechanism linked to metabolic status in breast cancer and the chemical synthesis of a novel class of inhibitors that target CtBP dimerization.
- In one of the largest clinical UK studies of its kind, we found that the strongest independent risk factor for early patient death in oral cancer patients was a myofibroblast-rich stroma. This allows early identification of aggressive cancers and the specific mechanism through which cancer cells generate a stromal response capable of supressing adaptive immunity.
- We were the first to demonstrate functional polymorphism in the antigen processing enzyme ERAP1. This provided a mechanistic rationale for its association with diseases such as ankylosing spondylitis, psoriasis and cervical cancer.
Collaborations and enterprise
- We have taken 12 reagents (DNA vaccines, monoclonal antibodies, and radioimmunoconjugates) from our own laboratories into clinical trials, with support from pharma, biotech, research council and charity funding.
- We were one of the first to identify immunostimulatory mAb and have gone on to deliver a first-in-man anti-CD40 mAb, ChiLob-7-4, now entering phase II trials.
- With CRUK, we have also established an antibody discovery programme to generate a pipeline of immunostimulatory reagents, which target the immune co-receptors of the TNFR superfamily. The first, an anti-CD27, has been developed in partnership with Celldex therapeutics, and is now in phase I trials. Our work on the mechanism of anti-CD20 immunotherapy has led to a new collaborative initiative with the Swedish Biotech company: BioInvent.
- We were the first to define the immunological functions for the MHC I cofactors calreticulin and tapasin, and the first to relate these to the generation of immunodominance to experimental vaccines. In collaboration with Microsoft, we have developed a new computational model that will help predict the immunological outcome of various immunotherapeutic approaches.
