"Spatial biology of clinical samples reveals mechanisms of treatment resistance to a novel CAR T-cell therapy “

CAR T-cell therapy faces several challenges in solid tumors, including lack of safe, uniformly expressed targets. To address this need, we investigate cell surface antigens directly upregulated by oncogenic gene fusions as a novel target class. We identify GPNMB as a promising target and develop a novel CAR T-cell therapy that demonstrates both safety and anti-tumour activity in a first-in-human clinical trial in sarcoma.

We use computational approaches to investigate CAR T-therapy resistance mechanisms with spatial transcriptomics on biopsies from resistant lesions collected on-trial, and identify  strategies to overcome resistance to test in next generation therapies.