The Fernandes Group focusses on dissecting and manipulating immune receptor signalling and developing methods to identify targets of immune recognition. Ricardo Fernandes has now been awarded a Cancer Research UK Immunology Project Award to continue these studies. In particular, he will be looking at characterising T cell receptor sequences that display anti-tumour responses and checking how these could cross-react to non-tumour antigens.
T-cell receptors are expressed on the surface of T cells and recognise peptides displayed on the cell surface of other cells to trigger activation of the T cell. If the peptide is recognised as foreign, such as those from bacteria or viruses, the T cell will become activated. In some cancers, there are peptides that are specific to the tumour, but these are often very similar to natural peptides in the body (termed cross-reactivity) and so T cells either do not recognise them as bad or they start to recognise the natural peptide as bad as well causing toxicity.
In this newly funded project, the Fernandes group will engineer tumour specific TCRs and determine their cross-reactivity to host peptides before combining these with other engineered receptors to sensitise T cell responses against tumours. They anticipate that these results will inform the development of cell-based therapies for eliciting robust antitumour T-cell responses.
Ricardo obtained his PhD at Oxford, working with Simon Davis on the mechanism of TCR triggering. Later he moved to Stanford for his postdoctoral studies, where he developed novel bispecific proteins that take advantage of endogenous membrane phosphatases to shut down signalling by surface receptors. The Fernandes' Lab applies protein engineering to decipher functional and structural correlates of immune receptor signalling and identify new therapeutic approaches to modulate T cell function in autoimmune, infection and cancer settings.