Cell Metabolism: Chen Sidi's team used CRISPR screening to discover new ways to enhance the effect of CAR-T

CAR-T cell therapy harnesses the immune response to cancer by introducing tumor-detecting molecules into T cells

On March 10, 2022, the team of Associate Professor of Genetics at Yale University, Sidi Chen , published a paper entitled: A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance Research paper on CAR-T therapy

Using CRSIPR screening technology, the study discovered a way to boost tumor-attacking T cells, a discovery that promises not only to improve the effectiveness of a promising cell-based cancer immunotherapy, but also to expand the cancers it can treat quantity

The Sidi Chen lab devised an ingenious method to efficiently scan the genome of CD8 T cells and unbiasedly identify (look for) genes that might enhance their function

"We developed a novel genome-wide gain-of-function screen to discover molecular enzymes that act like stepping on the gas pedal to increase metabolic activity in T cells," said Professor Chen

They found that high activity of several genes, including PRODH2, stimulated increased CAR-T cell activity in mouse models of three different types of cancer, including solid tumor breast cancer

Using these systems and findings, future studies can test novel metabolically enhanced CAR-Ts in clinical settings, identify other T-cell superchargers, and expand to different cancer types, especially solid tumors

Ye Lupeng, Jonathan Park, Peng Lei and Yang Quanjun from Yale University are the co-first authors of the paper, and Chen Sidi is the corresponding author

Original source:

Lupeng Ye, et al.