Our research - University of Birmingham

Cancer-targeted immunotherapies, both cellular and antibody-mediated, are poised to deliver transformative improvements in cancer treatment, with significant advances already evident in haematological and solid tumours. Fundamental research in the Cancer Immunology and Immunotherapy Centre (CIIC) is focused on three key themes, each critical to development of such novel treatments.

Research is focused on a small number of key themes which address fundamental issues in tumour immunology: understanding the tumour microenvironment; target identification, disease positioning, and clinical diagnostics; and immunotherapy development. Clinically these efforts are concentrated on haematological malignancies and solid tumours.

Academic research themes

Target identification, disease positioning, and clinical diagnostics

We are identifying and characterising new therapeutic targets, and exploring their therapeutic tractability in preclinical models.

In addition, we are exploring how to best exploit known targets, including determining which cancers and patient subgroups are most applicable. Finally, we developing new clinical biomarkers to optimise cancer diagnosis and also to guide treatment selection by detection of minimal residual disease.

Tumour microenvironment

The tumour microenvironment can be strongly immunosuppressive, and represents a potential axis for therapeutic intervention, and patient stratification. CIIC members are focussed on understanding and therapeutically exploiting the microenvironment to improve cancer therapies.

Immunotherapy development

CIIC members are focused on developing immunotherapeutic strategies based on key approaches such as vaccination, chimeric antigen receptors, adoptive transfer, TCR gene transfer, and combination approaches, several of which are currently in clinical trials.

Clinical research themes

Solid tumours

Development of immunotherapy programmes focussed on specific solid tumours where there are strong clinical academic teams is a major focus for the CIIC.

The over-arching aims of our clinical research programmes in solid tumours are to understand how immune responses in patients can affect both prognosis and response to treatment, to define which sets of patients are likely to benefit from new immunotherapy treatments, and develop and test new ways to exploit the immune system to more effectively eradicate tumour cells.

Specific areas of interest include therapeutic targeting of the tumour microenvironment, targeting of immunosuppressive populations, development of novel cancer vaccination approaches, antibody arming strategies, and development of personalised immunotherapy approaches, including checkpoint blockade.

Our solid tumour clinical trials portfolio addresses several of these therapeutic concepts, which synergise strongly with our fundamental research on tumour antigen selection, tumour microenvironment, and immunotherapeutic strategies.

The clinicians and researchers focussing on this area are based at the Queen Elizabeth Hospital Birmingham, Birmingham Children’s Hospital, the Institute of Cancer and Genomic Sciences, and the Institute of Immunology and Immunotherapy.

Haematological malignancies

Haematological malignancies are an area of major focus for the CIIC. Our strong translationally-oriented research programme aims to understand how immune responses can affect current treatment outcome, and how they can be exploited to more effectively eradicate tumour cells.

The research grouping, based at the Centre for Clinical Haematology and the Institute of Immunology and Immunotherapy, has been designated a Leukaemia and Lymphoma Centre of Excellence, and focusses both on stem cell transplantation and also development of novel chemotherapy regimens.

Research spotlight

Our spotlight showcases our innovative and pioneering research into cancer immunology.

Cutting off the supply lines for cancer, Dr Steve Lee and Professor Roy Bicknell

For a tumour to grow it needs to induce new blood vessel formation to maintain a supply of nutrients and oxygen. However the blood vessels that form in tumour tissue are different from those that supply healthy tissues, both in their appearance and the genes that they express. Consequently, genes that are selectively turned on in the tumour vasculature are potential targets for therapy. We are targeting the product of one such gene, a protein known as CLEC14A. We have conducted extensive analyses on the expression of this gene in healthy and tumour tissues, and found it to be highly expressed in the vasculature of several solid human tumours. In contrast, in healthy tissues it is absent or expressed at very low levels.

To target CLEC14A on the tumour vasculature, we are using the body’s immune system. More specifically, we are taking T lymphocytes from the blood and genetically engineering them to stably express a Chimeric Antigen Receptor (CAR) that specifically binds CLEC14A. T cells expressing other types of CARs have been shown to be very potent killers, and are already proving highly effective at destroying some forms of leukaemia. Therefore by engineering T-cells to express a CAR specific for CLEC14A, we hope to selectively destroy the blood vessels that supply tumour tissues, and in so doing, inhibit tumour growth.

Having engineered T-cells to express our CAR, we have shown that when they encounter cells expressing the CLEC14A marker, not only do the T-cells proliferate and make cytokines such as interferon gamma, but they also kill the CLEC14A expressing target cell. Fortunately CLEC14A is well conserved between mouse and humans, and our CARs are able to respond to this protein in both species. Therefore as we seek to develop this approach as a therapy for cancer patients, we have explored both the safety and efficacy of our engineered CAR T-cells in mouse cancer models. These studies have shown that not only is the approach safe, but it is also effective, inhibiting tumour growth in 3 different mouse models of solid cancer.

We are currently working with the Cell and Gene Therapy Catapult (London, UK) and have set up a spin out company (Chimeric Therapeutics Ltd) to develop this towards Phase 1 clinical testing.