Immunotherapies have demonstrated impressive results in the fight against cancer, especially the chimeric antigen receptor (CAR) T cell approaches. These involve collecting T cells from a patient, genetically engineering them with a receptor that helps recognize and destroy cancer cells, and then infusing them back. Unfortunately, many patients don’t produce enough T cells, leaving them unable to take advantage of these treatments.
UCLA researchers have developed a method of creating pluripotent stem cells virtually indefinitely in the laboratory. These special cells can give rise to every cell type in the body, including T cells. Their technique relies on artificial thymic organoids which mimic the environment of the thymus, the organ in which T cells develop from blood 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”, explained Dr. Gay Crooks, professor of pathology and laboratory medicine.
T cells are essential for the immune system in fighting infections, but also have the potential to eliminate cancer cells. Combined with gene editing approaches, this technique could allow the creation of unlimited T cells able to be used across large numbers of patients, without the need to use a patient’s own T cells.
“Once we create genetically edited pluripotent stem cell lines that can produce tumor-specific T cells in artificial thymic organoids, we can expand those stem cell lines indefinitely”, noted Amélie Montel-Hagen, the study’s first co-author.
One of the last issues that remain to be addressed is that the T cells produced using the artificial thymic organoids exhibit additional molecules on their surface that are not matched to each individual patient. Those extra molecules could lead to rejecting the transplanted cells.
“Our next step will be to create T cells that have the receptors to fight cancer but do not have the molecules that cause the rejection of the cells, which would be a major step toward the development of universal T cell therapies”, added Dr. Christopher Seet, study lead investigator and clinical instructor in the division of hematology-oncology at UCLA.
This approach could lead to novel cancer immunotherapy strategies but also spur further research on T cell therapies for viral infections and autoimmune diseases.
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