Naturally occurring T cell mutations enhance engineered T cell therapies. (https://pubmed.ncbi.nlm.nih.gov/38326614/)

These scientists wanted to find a way to make cancer treatments using T cells even better. T cells are special cells in our body that help fight off diseases, including cancer. Sometimes, these T cells are taken from a person's body and used as a treatment for their cancer. But sometimes, these treatments don't work very well because the T cells don't stay in the body for a long time or they don't work as well as they should.

So, the scientists decided to study some special mutations in T cells that are found in people with a type of skin cancer called cutaneous T cell lymphoma. These mutations help the T cells in those people fight the cancer better.

The scientists tested 71 different mutations in T cells to see how they affect the T cells' ability to fight cancer and how long they stay in the body. They found one mutation called CARD11-PIK3R3 that made the T cells work even better against cancer. This mutation improved the communication between different parts of the T cells and made them more effective at killing cancer cells.

The scientists also wanted to make sure that using these mutated T cells would be safe. So, they followed the T cells with the CARD11-PIK3R3 mutation for a long time after they were put back into the body. They found that these mutated T cells did not turn into cancer cells themselves and they stayed in the body for a long time without causing any harm.

Overall, the scientists discovered that using naturally occurring mutations in T cells can make cancer treatments using T cells much better. This could help many more people with cancer in the future.

Garcia J., Daniels J., Lee Y., Zhu I., Cheng K., Liu Q., Goodman D., Burnett C., Law C., Thienpont C., Alavi J., Azimi C., Montgomery G., Roybal KT., Choi J. Naturally occurring T cell mutations enhance engineered T cell therapies. Nature. 2024 Feb 7. doi: 10.1038/s41586-024-07018-7.