Ultra-sensitive CAR T cells eliminate solid tumours in mice

Engineered ultra-sensitive CAR T cells that detect very low levels of the CD70 antigen eliminated kidney, ovarian and pancreatic tumours in mice; the researchers plan to seek funding for a phase I safety trial in humans.

Researchers report that engineered immune cells eliminated kidney, ovarian and pancreatic tumours in mice. The cells were designed to detect extremely low levels of a protein called CD70, which the study reports is present on all cancer cells in some solid tumours but often at very low amounts. The work, published in Science, combines a synthetic chimeric antigen receptor with a natural T cell receptor to create a CD70-targeted HLA-independent T cell (HIT) receptor. The team is preparing to seek funding for a phase I safety trial in humans. Key findings: - Ultra-sensitive CAR T cells cleared kidney, ovarian and pancreatic tumours in mouse models. - CD70 was reported as expressed on 100% of cancer cells in some tumours, but often at levels undetectable by standard tests. - The CD70-targeted HIT receptor fuses a synthetic CAR with a natural T cell receptor and increases internal signalling to respond to very low antigen amounts. - The engineered cells were described as able to detect antigen concentrations about 10–50 times lower than current cellular therapies. - Analysis of a single-cell atlas across roughly 30 tissue types found oesophageal epithelial cells as the only non-immune healthy cells with low CD70 expression (about 3% of those cells). - Fewer than 5% of T and B immune cells were reported to express CD70, and the authors noted a need to evaluate possible off-target effects in human trials. Summary: The study presents an approach intended to reduce antigen escape by targeting cells with very low antigen expression. The authors plan to seek funding for a phase I safety trial and have highlighted the importance of carefully assessing potential off-target effects on immune and oesophageal cells. Undetermined at this time.