Projects

Here are a few examples of project areas that we are currently working on

Improving immunotherapy for solid cancers

Cancer incidence is rising, and there are few options for patients whose disease becomes resistant to conventional chemotherapy or radiotherapy. Immunotherapy offers some hope, but there is a need for an effective cell therapy platform to treat solid cancers. Whilst immunotherapy using T-cells engineered to express synthetic molecules such as chimeric antigen receptors (CARs) has revolutionised the treatment of lymphoid malignancies, results against solid cancers have been less promising. The fundamental barriers of tumour homing, the immunosupressive microenvironment and immune quorum have not yet been overcome.

Immunomodulatory payload delivery using γδT

TRIS-γδ is a next-generation, allogeneic T-cell therapy platform designed to overcome the well-recognised limitations of solid cancer targeting. It uses an alternative cell chassis which can be safely manufactured in batches and given to multiple patients. TRIS-γδ not only has anti-cancer activity in of itself, it also recruits bystander immune cells to attack the tumour. The Fisher Lab is developing this platform technology to target a range of adult and paediatric cancers including colorectal cancer and osteosarcoma.

Modelling immunotherapy in biomimetic 3D systems

Inter-species differences in γδT cell biology complicate in-vivo studies of γδT activity. The Fisher Lab therefore uses fully human culture systems comprising 3D tumour models combined with engineered γδT cells. By subjecting these to high-parameter analysis we are able to characterise the mechanism of action of novel constructs in a relevant tumor context. In collaboration with Dr Chris Tape at the UCL Cancer Institute we are exploring novel immunotherapies for colorectal cancer. We are also developing similar model systems for the development of osteosarcoma immunotherapy.

Efficient and modular cell engineering

Regardless of the expression cassette, viral manufacture remains one of the single biggest costs in cellular immunotherapy. We aim to develop substantially more efficient means of engineering γδT cells to express bicistronic or tricistronic cassettes. This will be of benefit not only to our own work, but also to others who wish to harness the unique properties of this immune subset for immunotherapeutic development.