Transcription factors protect anti-cancer CAR-T cells from depletion

Researchers at the La Jolla Institute of Immunology (LJI) have demonstrated how to design anti-cancer T cells to clear tumors without succumbing to T cell exhaustion, a phenomenon that causes T cells to abandon the fight against tumors after prolonged overactivity.

LJI professor Dr.

Fighting tumors is a marathon, not a sprint

In order to produce CAR-T immunotherapy, researchers extracted T cells from cancer patients and effectively "armed" them by changing the expression of genes that help fight cancer

Both treatments may cause T cell failure

In their new study, the researchers aim to solve the problem of fatigue by giving T cells the ability to fight fatigue itself

Their research on mouse melanoma and colorectal cancer tumor models showed that changing CAR-T cells to overexpress BATF can lead to tumor clearance without causing T cell failure

Further testing showed that although IRF4 is important, it should not be overexpressed like BATF

"Not only did we improve the ability of T cells to fight fatigue, we also improved the ability of cells to fight tumors," said Edahí González-Avalos, co-first author of the study, a graduate student in Rao's lab who led the project Bioinformatics analysis

The LJI team believes that a promising strategy is to combine these methods with targeted transcription factors to make T cells resistant to depletion

The researchers emphasized that BATF is just one of many transcription factors that may play an important role in combating T cell failure