UCL researchers have created an artificial thymus organoid capable of producing specialised T-cells
The small organ called the thymus plays a central role in the creation of T-cells to support the immune system. Unfortunately, we we age the thymus shrinks gradually and its ability to field these cells falters. T-cells can become specialised through the addition of different receptors on their membrane - each able to pick up and target different antigens. This ability did not go unnoticed by cancer researchers, who designed a treatment called CAR-T cell therapy; an immunotherapy strategy that involves engineering T-cells to express a specific chimeric receptor locked on to a certain antigen on cancer cells.
The immunotherapy approaches can in some cases use a patient's own cells, also called adoptive T-cell therapy. This involves editing a patient's own cells before reinfusing them back into them. Understandably, this can be time consuming and many individuals simply don't have a healthy enough immune system to supply enough cells for an effective treatment. An alternative approach is therefore to use a stem cell derived population or a donor supplied population - neither of which are perfectly matched to the patient which can in some cases cause severe complications. This means there is a sore need for greater production capacity alongside reduced risk of immunogenicity (harmful immune reaction).
"We know that the key to creating a consistent and safe supply of cancer-fighting T cells would be to control the process in a way that deactivates all T cell receptors in the transplanted cells, except for the cancer-fighting receptors"
An artificial thymus
A team at UCLA was able to build a thymus organoid structure with an ability to form T-cells from blood stem cells. What's more, the produced cells resembled natural T-cells, with a diverse range of receptor types. When the researchers added an additional gene for a specific, cancer targeting receptor they found many of the newly produced cells retained this receptor while shedding many of the other types. This means that they may be able to hone in on the cancer without causing collateral damage to healthy tissue too. Due to the success of the research, the team is looking to incorporate pluripotent stem cell technology to expand and optimise their approach, with the hope of providing a fresh source of T-cells for cancer patients in need.
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