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White blood cells such as T cells continuously patrol the body in search of abnormal cells, such as infected or cancerous cells. T cells detect molecules called ‘antigens’ on the surface of abnormal cells using their T cell antigen receptors (TCRs). T cells are remarkably sensitive: they can become activated by the presence of a single antigen on a cell. This sensitivity is important because infectious organisms and cancer cells are very good at hiding from T cells by lowering the amount of antigen on the cell surface.

An exciting new treatment for cancer is to redirect T cells to target a patient’s cancer cells. This is done by using genetic engineering to express chimeric antigen receptors (CARs) on T cells. CARs have an extracellular part that binds a target antigen on the cancer cell and an intracellular part derived from the TCR that send an activating signal into the T cell. The antigens that CARs target on cancer cells cannot normally be recognised by TCRs, which is why CARs effectively re-direct and boost a patient’s T cells to kill cancer cells. This therapy is very effective for targeting antigens expressed at high levels on leukaemias and lymphomas. However, many patients relapse when cancer cells emerge that have lower levels of antigen on their surface. One reason why this escape is possible is that CARs are not very sensitive and so are unable to ‘see’ these new cancer cells. There is an urgent need to increase the sensitivity of CARs to prevent these relapses. More sensitive CARs would also allow CAR T cells to be used in treating a wider variety of cancer antigens that are expressed at low levels.

In new work, Burton et al (2025) have now engineered CAR-T cells to display ultra-high antigen sensitivity that can match the sensitivity of the TCR. This was achieved by engineering elongated variants of the adhesion receptor CD2 or by reducing the physical size of standard CARs.

To exploit these technologies for optimising CAR-T cell sensitivity, Prof Dushek and Prof Anton van der Merwe have founded a spinout company, MatchBio Ltd. While improved CARs will transform the treatment of cancer, they may also prove useful for treating intractable infections and autoimmune disease.

The new paper can be found on Biorxiv

Listen to Prof Dushek discuss this paper and the formation of the new spin-out MatchBio in this podcast.