Team/Members of the group:

• Margaret Dunne, Postdoctoral researcher 
• Nawal Taher, PhD student 
• Gráinne Jameson, PhD student 
• Stefan Elekes, Laidlaw Scholar 
• Sinead Cummins, Laidlaw Scholar 

Close Collaborators:

• Eleanor Molloy
• Joanne Lysaght
• Clair Gardiner
• John Reynolds
• Nicola Gardiner
• Joseph Keane
• Aideen Long 

Main Funders: 
Irish Blood Transfusion Service

Active research programmes: 
The Cellular Immunology group at TTMI is focussed on the roles and treatment potential of innate T lymphocytes for cancer.  Cellular therapies involving two subsets of innate T cells - natural killer T (NKT) cells and gamma/delta (γδ) T cells are under intensive investigation in clinical trials, while another class of innate T cells - mucosa-associated invariant T (MAIT) cells – are showing anti-tumour efficacy in preclinical studies.  Innate T cells are promising candidates for tumour immunotherapy because they are not MHC-restricted and therefore will not cause allogeneic tissue rejection, meaning that the cells from one donor can be used as an ‘off-the-shelf’ therapy for multiple patients.  Furthermore, innate T cells can be engineered to express chimeric antigen receptors (CARs), thus combining their anti-tumour activities with the tumour targeting capacities of CAR-T cells.

In collaboration with clinicians, scientists and industry partners, we are investigating the biology of NKT cells, γδ T cell subsets, and MAIT cells in healthy donors and patients with lung, oesophageal, gastric, liver, colorectal and blood cancers.  We found that many innate T cell subsets are depleted in the cancer patients.  We identified novel stimulatory ligands and conditions that promote their anti-tumour activities.  We also have identified mechanisms by which innate T cells activate the anti-tumour activities of other immune cells and how they can be grown under good manufacturing practice (GLP) conditions for clinical use.

Our expertise covers a range of cellular immunological techniques involved in the isolation, expansion and functional characterisation of human innate T cells and the optimisation of their anti-tumour activities.  We propose to answer the following key questions:

• Which innate T cell subsets provide the best protection against which cancer types?
• How can the anti-tumour efficacies of innate T cell therapies be improved? Specifically, how can we enhance tumour recognition, targeting, infiltration, killing and recruitment of other immune cells?  
• Related to the question above, how can we best generate CAR-innate T cells?
• How can innate T cell subsets optimally be expanded to sufficient numbers under GLP conditions?

How can we best we translate these finding into clinical trials at St James’s Hospital?