Tailored Thymus Organoids Produce Specifically Configured T Cells

The thymus atrophies considerably following childhood, and then declines further in old age. This organ is where the immune cells called T cells mature, and its decline limits the pace at which new T cells are generated. The slow and faltering rate of immune cell creation is one of the contributing factors to immune system aging; it effectively caps the number of cells present in the body, and that population becomes ever more misconfigured due to exposure to persistent pathogens such as cytomegalovirus. Expanding the supply of immune cells should help to restore some of the lost immune function in older people, and engineering additional thymus tissue for transplantation is one possible approach to this goal. Researchers are making good progress in generating small amounts of functional thymus tissue. As this research demonstrates, the scientific community is now able to adjust the resulting tissue in order to generate T cells with specific desired characteristics.

Researchers have created a new system to produce human T cells, the white blood cells that fight against disease-causing intruders in the body. The system could be utilized to engineer T cells to find and attack cancer cells, which means it could be an important step toward generating a readily available supply of T cells for treating many different types of cancer. The thymus sits in the front of the heart and plays a central role in the immune system. It uses blood stem cells to make T cells, which help the body fight infections and have the ability to eliminate cancer cells. However, as people age or become ill, the thymus isn't as efficient at making T cells.

T cells generated in the thymus acquire specialized molecules, called receptors, on their surface, and those receptors help T cells seek out and destroy virus-infected cells or cancer cells. Leveraging that process has emerged as a promising area of cancer research: Scientists have found that arming large numbers of T cells with specific cancer-finding receptors - a method known as adoptive T cell immunotherapy - has shown remarkable results in clinical trials. Adoptive T cell immunotherapy typically involves collecting T cells from people who have cancer, engineering them in the lab with a cancer-finding receptor and transfusing the cells back into the patient.

Since adoptive T cell immunotherapy was first used clinically in 2006, scientists have recognized that it would be more efficient to create a readily available supply of T cells from donated blood cells or from pluripotent stem cells, which can create any cell type in the body. The challenge with that strategy would be that T cells created using this approach would carry receptors that are not matched to each individual patient, which could ultimately cause the patient's body to reject the transplanted cells or could cause the T cells to target healthy tissue in addition to cancer cells.

Researchers used a new combination of ingredients to create structures called artificial thymic organoids that, like the thymus, have the ability to produce T cells from blood stem cells. The scientists found that mature T cells created in the artificial thymic organoids carried a diverse range of T cell receptors and worked similarly to the T cells that a normal thymus produces. The researchers now are looking into using the system with pluripotent stem cells, which could produce a consistent supply of cancer-fighting T cells for patients in need of immediate life-saving treatment.

Link: http://newsroom.ucla.edu/releases/artificial-thymus-developed-at-ucla-can-produce-cancer-fighting-t-cells-from-blood-stem-cells


From the headline they seem to want to use an engineered thymus to produce T cells to fight cancer. Is this a better approach than extracting T cells from a blood draw and then gentleridally engineering a car receptor and re-infusing them? I can't really see the advantage?

Posted by: Jim at April 6th, 2017 2:31 PM

Wow, this is a great step forward against the aging of the immune system!

Posted by: Antonio at April 6th, 2017 3:37 PM

Jim: It's explained in the link. First, some cancer patients don't have enough T cells to begin with. Second, T cells that matured in the organoid have all receptors turned off / eliminated except for the engineered receptor.

Posted by: Antonio at April 6th, 2017 3:46 PM

Why stop at cancer, why not use this to make replacement Thymus and solve a major piece of the aging puzzle?

Posted by: Steve Hill at April 7th, 2017 6:09 AM

@Antonio - well t cells extracted from the patient have already been through negative selection in that patients thymus anyway, so won't have autoreactive TCRs.

I suppose it could be useful for very sick (post chemo) or young patients who don't have many t cells.

I think a more interesting application might be as an augmented immune system, rather than just as an alternative source of chimeric antigen receptor t cells. Just produce lots and lots regular t cells and inject them. More chances that one of these t cells reacts to a cancer neo antigen.

I've got to wonder how long it takes to engineer a patient matched artificial thymus from each patient though? Days? Weeks? Months?

Posted by: Jim at April 8th, 2017 12:00 AM

Very interesting! All we really need from this to make a full Thymus replacement is a way to selectively deactivate self-receptors.

Posted by: Patrick at April 12th, 2017 12:40 PM
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