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Erina He
Treatments involving the use of the body's immune system to fight cancer have led to significant improvements in patient survival in recent years, particularly using a method called CAR T-cell therapy. This treatment involves extracting a patient's own T-cells and modifying them in a lab to express a special receptor called a Chimeric antigen receptor (CAR) that recognises a tumour protein. These are then reinfused back into the patient, where they can find and destroy cancer cells.
However, while CAR T-cells have shown great promise for the treatment of blood cancers, they have struggled to effectively target solid tumours. CARs are unable to easily distinguish tumour cells from healthy cells that have the same target protein, which is a major issue when treating solid tumours as the healthy tissue surrounding a solid cancer is often critical for survival but express similar proteins to the tumours themselves.
In contrast, natural T-cells with T-cell receptors (TCRs) are better able to discriminate between tumour cells and healthy cells. However, TCR-based therapies often suffer from limited effectiveness against tumours.
Researchers at the Kennedy Institute of Rheumatology at the University of Oxford in collaboration with the National Cancer Institute (NCI) and the University of Montréal, therefore set out try to combine these approaches to overcome these limitations.
Sooraj Achar, a NIH/Oxford graduate student at the Kennedy Institute, and Dr. Taisuke Kondo, a postdoctoral research fellow at NCI, worked together to create cells expressing both a TCR and a CAR. They characterised their responses to hundreds of ligand combinations using both the high throughput IMMUNOtron robotic platform and animal models. Surprisingly, the data they collected suggested that weak TCR signals inhibited CAR activity.