Swiss scientists have developed a new method to switch off Chimeric Antigen Receptor (CAR)‑T cell therapy to prevent it from damaging healthy tissue.
Their new method could potentially be used to switch off the modified T cells on command to prevent severe side-effects, such as cytokine release syndrome. The scientists, led by Dr Bruno Correia at the Ecole Polytechnique Federale de Lausanne in Switzerland, say it acts like an “emergency safety net for patients who respond badly to treatment”.
The team have successfully tested their approach in mice infused with prostate cancer cells. It could allow the use of CAR‑T cell therapies in situations which are currently thought to be too risky, the researchers say.
Details of the system, known as STOP-CAR, were published last week in Nature Biotechnology.
The researchers used computational protein design to re-engineer the chimeric antigen receptors. This meant that when T-cells transduced with these CARs were reinfused to the patient, the signal generated when it binds to a tumour antigen can be switched off, “effectively disabling the T-cell."
Dr Correia says: “The real advantage of this system is that we can switch the T-cell back on again if we stop administering the molecule. There’s no need to destroy the T-cells if they pose a threat to a patient’s health. The system lets us precisely control the effects of immunotherapy.”
Co-author Dr George Coukos adds: “This work itself, and its potential, is really exciting, but I think it is also illustrative of how well-orchestrated, multidisciplinary collaborations can yield significant scientific breakthroughs.
“We hope to bring STOP-CAR-T therapy as quickly as possible to cancer patients.”
Giordano-Attianese G, Gainza P, Gray-Gaillard E, Cribioli E, Shui S, Kim S, Kwak MJ, Vollers S, Corria Osorio AJ, Reichenbach P, Bonet J, Oh BH, Irving M, Coukos G, Correia BE (2020) “A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy”, Nature Biotechnology, doi: 10.1038/s41587-019-0403-9