Senescence

Immune Cells Can Be Engineered to Kill ‘Zombie Cells’ That Contribute to Ageing

Posted on 23 June 2020

Events such as damage to the DNA can cause a cell to enter senescence – a state of dormancy in which it can no longer divide to produce new cells. Senescence is thought to be key to the ageing process – not only do accumulating senescent cells act as ‘dead weight’ within tissues, but they can also release harmful signalling molecules that promote the development of age-related diseases. Scientists have been interested in the possibility of using senolytic drugs – drugs that remove senescent cells – in order to slow or reverse some aspects of ageing.

Now, researchers at Memorial Sloan Kettering have developed a way to remove senescent cells by repurposing an existing therapy used to treat cancer. In Chimeric Antigen Receptor (CAR) T cell therapy, T cells are removed from the patient and genetically engineered to produce a receptor that will recognise the patient’s cancer. These cells are then reintroduced into the patient, and are able to selectively seek out and kill cancer cells.

In this study, researchers managed to identify a molecule called urokinase plasminogen activator receptor (uPAR) that is predominantly present on the surface of senescent cells. They then engineered CAR T cells to recognise this molecule, and found that the T cells could effectively eliminate senescent cells in mice, and also improved the survival of mice taking senescence-inducing chemotherapy.

Fluorescent image of CAR T cells in mouse liver fibrosis
CAR-T cells (red) attack senescent cells (green) in liver tissue

The next step will be to determine if these CAR T cells can also combat senescence -associated diseases like atherosclerosis and diabetes, with the ultimate aim of employing the treatment in humans.

This study demonstrates that T-cell engineering and CAR therapy can be effective beyond cancer immunotherapy. We think this approach has the potential to tackle a number of senescence-related diseases for which new treatments are badly needed.

A New Target for CAR T Cells: Senescence-Related Diseases. (2020). Retrieved 23 June 2020, from https://www.mskcc.org/blog/new-target-car-cells-senescence-related-diseases

References

A New Target for CAR T Cells: Senescence-Related Diseases: https://www.mskcc.org/blog/new-target-car-cells-senescence-related-diseases

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