Recharging for T cells
Researchers from Yale University have described a way to "recharge" the T-cells attacking the tumor. This discovery can not only increase the effectiveness of cancer immunotherapy, but also increase the number of oncological diseases that can be treated with CAR-T lymphocytes.
CAR-T therapy is based on the activation of its own immune system against cancer cells by introducing tumor-detecting receptors into lymphocytes. Over the past decade, the U.S. Food and Drug Administration has approved six CAR-T cell therapy methods for the treatment of B-cell lymphomas and multiple myeloma. But, despite the impressive success, the effectiveness of treatment tends to decrease over time, which marked the beginning of the search for ways to increase the activity of T cells. In addition, there are currently no approved CAR-T cell therapies for solid tumors.
For their research, the group developed a CRISPR-based method for effectively screening the CD8 T-lymphocyte genome for the presence of specific genes that could enhance their ability to attack cancer cells. The researchers found that the high expression of several genes, including the proline dehydrogenase 2 (PRODH2) gene involved in cellular metabolism, increases the activity of CAR-T cells in mouse models of three different types of cancer, including a solid tumor – breast cancer.
The results obtained show that it is possible to produce hyperactive CAR-T cells that are superior to existing cell therapy methods. In future studies, based on the developed technologies, it will be possible to test newly identified types of metabolically enhanced CAR-T lymphocytes in clinical settings, identify other methods of "recharging" T cells and test immunotherapy for various types of oncological diseases, including solid tumors.
Article L.Ye et al. A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy is published in the journal Cell Metabolism.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Yale University: Yale scientists'supercharge' cancer-fighting T cells.