Scientists have developed a new technique to turn pluripotent stem cells - which can give rise to every cell type in the body - into mature T cells capable of killing tumours.
The technique developed by researchers at the University of California, Los Angeles (UCLA) in the US uses structures called artificial thymic organoids, which work by mimicking the environment of the thymus, the organ in which T cells develop from blood stem cells.
T cells are cells of the immune system that fight infections, but also have the potential to eliminate cancer cells.
The ability to create them from self-renewing pluripotent stem cells using the new technique could lead to new approaches to cancer immunotherapy, according to the study published in the journal Cell 'Stem Cell'.
The advance could spur further research on T cell therapies for viral infections such as HIV, and autoimmune diseases, the researchers said.
Among the technique’s most promising aspects is that it can be combined with gene editing approaches to create a virtually unlimited supply of T cells able to be used across large numbers of patients, without the need to use a patient’s own T cells, they said.
T cell therapies, including CAR T-cell therapy, have shown great promise for treating certain types of cancer.
Current approaches involve collecting T cells from a patient, genetically engineering the T cells with a receptor that helps them recognise and destroy cancer cells, and then infusing the cells back into the patient.
However, engineered T cells do not always function well, treatment is expensive because it is tailored to each patient, and some people with cancer don't have enough T cells to undergo the therapy.
A technique that produces T cells without relying on collecting them from patients is an important step towards making T cell therapies more accessible, affordable and effective, researchers said.
"What's exciting is the fact that we start with pluripotent stem cells," said Gay Crooks, a professor at UCLA.
"My hope for the future of this technique is that we can combine it with the use of gene editing tools to create 'off-the-shelf' T cell therapies that are more readily available for patients," Crooks said.
The researchers previously demonstrated that the 3D structure of an artificial thymic organoid allowed mature T cells to develop from adult blood stem cells.
They also hypothesised that they would also support mature T cell production from pluripotent stem cells.
"The 3D structure of the artificial thymic organoid seems to provide the right supportive signals and environment needed for mature T cells to properly develop," Crooks said.
The research demonstrated that the artificial thymic organoids can efficiently make mature T cells from both kinds of pluripotent stem cells currently used in research: embryonic stem cells.
These cells originate from donated embryos, and induced pluripotent stem cells, which are created by reprogramming adult skin or blood cells back to an embryonic-like state.
The researchers also showed they could genetically engineer pluripotent stem cells to express a cancer-targeting T cell receptor and, using artificial thymic organoids, generate T cells capable of targeting and killing tumour cells in mice.
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