Hypoxia-Sensing CAR T-cell Immunotherapy
Genetically engineering a cancer patient’s T-cells to target cancer cells, known as ‘CAR T-cell immunotherapy’, has resulted in cures for some patients with certain blood cancers, but translating this success to solid tumours has proven challenging in large part due to a lack of tumour-specific targets to direct CAR binding. The Arnold lab with Dr John Maher’s team have been pioneering hypoxia-sensing CAR T-cells, coined ‘HypoxiCAR’, as a strategy to activate CARs specifically within the hypoxic tumour microenvironment. We have demonstrated using preclinical models of cancer that treatment with HypoxiCAR T-cells, despite the presence of the CAR target on normal tissues, circumvents on-target off-tumour activation and systemic cytokine storm while delivering anti-tumour activity.