Artificial Thymus Fabricates Cancer Fighting T-Cells From Stem Cells

A new strategy to produce human T cells has been developed by researchers at UCLA. T-cells are the white blood cells that fight against disease-causing intruders in the body.

The system could be used to engineer T cells to search for and destroy cancer cells. It could be a valuable step toward manufacturing a readily available supply of T cells for treating many different types of cancer.

The thymus, located in the front of the heart, plays an important 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. But as people grow older or become ill, the thymus isn’t as efficient at making T cells.

Adoptive T Cell Immunotherapy

In your body, T-cells produced by the thymus are assigned receptor molecules, which act as guides towards cells infected by viruses or cancers. Leveraging that process is emerging as a promising area of cancer research.

Scientists have found that arming large numbers of T cells with specific cancer-finding receptors — an approach known as adoptive T cell immunotherapy — has shown exceptional results in clinical trials. Adoptive T cell immunotherapy commonly 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.

The catch, which this new method attempts to fix, is that the treatments can be time-consuming, and people with cancer might not have enough T cells for the immunotherapy to work.

artificial thymic organoid

T cells (red) that were produced using artificial thymic organoids developed by UCLA scientists. Credit: University of California, Los Angeles

Senior author Dr. Gay Crooks, a professor of pathology and laboratory medicine and of pediatrics and co-director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, said:

“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.”

Artificial Thymic Organoids

This is crucial, as cells produced from stem cells not taken from the patients themselves present the risk they could be rejected once they’re in the patient’s body.

The UCLA researchers used a novel blend of ingredients to create structures called artificial thymic organoids that, like the thymus, have the ability to produce T cells from blood stem cells. 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.

When they inserted a gene that delivers a cancer-fighting receptor to the blood stem cells, they found that the thymic organoids produced large numbers of cancer-specific T cells, and that all other T cell receptors were turned off. The results suggest that the cells could potentially be used to fight cancer without the risk of T cells attacking healthy tissue.

Even better, the team says the system can readily be reproduced by other scientists who study T cell development. The UCLA researchers are now investigating 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.

Christopher S Seet, Chongbin He, Michael T Bethune, Suwen Li, Brent Chick, Eric H Gschweng, Yuhua Zhu, Kenneth Kim, Donald B Kohn, David Baltimore, Gay M Crooks & Amélie Montel-Hagen
Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids
Nature Methods (2017) doi:10.1038/nmeth.4237

Top Image: Peter Lane and Fiona McConnell, Wellcome Images

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