Immunology of virus-associated cancers:
Through collaborations with the Chinese University of Hong Kong (Prof. A.T.C. Chan, Prof. K.W. Lo) and University of Groningen, Holland (Dr A. Diepstra), we are investigating T cell responses to the EBV-associated cancers Nasopharyngeal carcinoma (NPC) and Hodgkin’s Lymphoma respectively. As part of our basic research into the immunology of these cancers, we are exploring immune evasion mechanisms and the function of T cells that naturally reside within the tumour tissue.
Engineering T cells for adoptive therapy approaches:
Having established the use of adoptive T cell therapy in Birmingham through a pilot study in which 6 cancer patients were safely infused with tumour antigen-specific T cell clones, we are currently developing a rapid and reliable approach to generate therapeutic T cells using T cell receptor (TCR) gene transfer. We have successfully cloned a gene encoding a TCR specific for LMP2, a viral protein widely expressed in EBV-associated tumours. Using retroviral mediated gene transfer we have then delivered this TCR into T cells. The result is that within 3-5 days we can reliably generate large numbers of high avidity LMP2-specific effectors capable of recognising cells endogenously expressing physiological levels of this viral protein.
In order to target more common non-virus associated malignancies, we have recently begun a project to express a chimeric antigen receptor (CAR) in T cells that will enable them to selectively attack the blood vessels that supply many human cancers (including breast, prostate, kidney and bladder cancer).
Furthermore we are exploring the use of engineered T cells derived from cord blood as a source of more effective anti-cancer cells.
T cell homing to tumour tissues:
If T cells are to be effective in treating cancer, they must be capable of homing to the tumour site. But they will only be recruited to a tissue if they express the appropriate selectins, integrins and chemokine receptors for engaging molecules presented at this site. Since many tumours (e.g. NPC, Hodgkin’s lymphoma and Renal cell carcinoma) are naturally infiltrated with T cells, another key area of our research is to define the mechanisms whereby these cells are recruited with a view to conferring the appropriate homing phenotype on tumour-specific effectors.