Lay summary
Cancer is the leading cause of mortality in Aotearoa, and innovative therapies are urgently needed. CAR T-cell therapies, whereby a patient’s own immune cells are engineered to recognise tumour-specific antigens, have been game-changing for lymphomas. However, they are largely ineffective against solid tumours, which don’t display antigens evenly and suppress immune cell activity. Chemotherapies don’t have this limitation, but are highly toxic to most immune cells, including CAR T-cells. To extend the range of CAR T-cell therapy to solid tumours, we will investigate the following research question: "Can CAR T-cells be protected from the toxic effects of anti-cancer drugs?" To address this, we will combine a bioinformatic approach with a powerful enzyme discovery pipeline to discover novel enzymes capable of defending CAR T-cells against the toxicity of chemotherapeutics. Lead enzymes will then be optimised by evolution-based engineering and evaluated in a co-culture model of CAR T and tumour cells.