T cells is a type of white blood cell that is of key importance to the immune systems and is at the core of adaptive immunity, the system that tailors the body’s immune response specific pathogens. The T cells are like soldiers that search out and destroy the targeted invaders, as well as eliminating cancer cells.
Studies by researchers of UCLA is the first to interpret a technique for coaxing pluripotent cells, which uses structures called artificial thymic organoids, which work by mimicking the environment of thymus, the organ in which T cells develop from blood cells.
This can give rise to every cell type in the body and which can be grown indefinitely in the lab into becoming mature T cells capable of killing tumor cells.
The success of this discovery can spur further research on T cells therapies for viral infections such as HIV.
T cells therapy, 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 recognize and destroy cancer cells, and then infusing the cells the cells back into the patient.
Therefore, a technique that produces T cells without relying on collecting them from patient is an important step forward toward making T cells therapies more accessible, affordable and reliable.
“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 shell T cell therapies that are more available for patients ,” Crook said, “What’s exciting is the fact we started with pluripotent stem cells.”
“Demonstrations by Crook and her team that the 3-D structure of an artificial thymic organoid allowed mature T cells to develop from adult blood stem cells, and hypothesized that they would also support mature T cell production from pluripotent stem cells.
“The 3-D structure of the artificial thymic organoid seems to provide the right supportive signals and environment needed for mature T cells to properly develop,” she 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, which 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 tumor cells in mice.
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,” said Amélie Montel-Hagen, the study’s first co-author and an associate project scientist in Crooks’ lab. Having an unlimited supply of T cells capable of fighting various types of tumors would be a major turning point for cancer treatment.
One of the remaining challenges for the UCLA scientists is that the T cells created using the artificial thymic organoids have additional molecules on their surface that are not matched to each individual patient. Those extra molecules could cause a patient’s body to reject the transplanted cells, Montel-Hagen said.
“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,” said Dr. Christopher Seet.
: University of California, Los Angeles