Professor Hayday studied biochemistry at Cambridge and was awarded a PhD in tumour virus genetics at Imperial College London. After moving to MIT [1982], he co-discovered genes defining a novel and unanticipated lymphocyte compartment called gamma delta (gd) T cells. On the faculty at Yale and following his move back to London, Professor Hayday showed that gd T cells were unique; that mice lacking gd T cells were highly susceptible to skin cancer; and that gd T cells possess unique mechanisms to discriminate healthy from transformed cells, thereby creating a natural therapeutic window. Building on the cells’ potential as Immunotherapeutics, Professor Hayday spun-out two companies, “Gamma Delta Therapeutics” and “Adaptate” which initiated clinical trials in refractory leukaemia before acquisition by Takeda. Additionally, Professor Hayday showed, based on human genetics, that gd T cells have potentially therapeutic roles in Crohn’s Disease. Professor Hayday won the DeVane Medal, Yale College's most prestigious prize for scholarship [1997]; was elected to lead the British Society of Immunology [2005-2009]; has chaired numerous funding committees; was elected Fellow of the Academy of Medical Sciences [2002] and the Royal Society [2016]; and received an honorary degree from Heidelberg University [2022]. He also has a keen interest in human immune-profiling, believing that when this is accomplished at scale it can greatly enhance the targeting of immunotherapies and surveillance of immune-related diseases.

Immunotherapy has transformed our view of how the host responds to cancer, with game-changing impacts on patient treatment and management. Despite immense successes, the focus on MHC-restricted ab T cells as the therapeutic modality comes with considerable challenges, including a common loss of MHC by cancer cells, the difficulty in seeing tumours of low mutagenic burden, the refractoriness of immunosuppressive tumour microenvironments, and substantial adverse events that can likewise apply to ab CAR-T cells. By contrast, these issues are less relevant to gd T cells, an evolutionarily conserved lymphocyte subset displaying several unique traits that make them excellent, practical candidates for greatly extending the reach of immunotherapies. Indeed, the lecture will consider newly obtained data that identify the gd T cell receptor (TCR) as a critical, real-time determinant of tissue surveillance that deploys a unique molecular mechanism to discriminate healthy cells from cancer cells. This discrimination creates a natural therapeutic window, offering immunotherapeutic efficacy against a background of rare adverse events. Data presented will span basic biological studies and clinical trials.