A Master Regulator of Gene Expression

Researchers used a CRISPR-based platform to identify master regulators of T cell function.

Immunotherapies such as chimeric antigen receptor (CAR) T cell therapy are promising approaches in the fight against cancer. How well the therapies work depends on T cell function, which is determined by the network of genes that these immune cells express. Recently, researchers at Duke University developed a CRISPR-based screening platform to identify key epigenetic regulators of human T cell function, and discovered the central role of the transcription factor Basic leucine zipper transcription factor ATF-like 3 (BATF3) in reprogramming the expression of several genes and improving the efficacy of CAR T cells in eliminating cancer cells. Their findings, published in Nature Genetics, may aid in the development of more effective T cell-based immunotherapies.

“It’s a very elegant study. It’s really interesting to see how this field of CRISPR screen is developed here using primary human T cells, which are not the easiest to work with,” said Fredrik Wermeling, an immunologist at the Karolinska Institute who was not involved in the research.

For years, biomedical engineer and study author Charles Gersbach from Duke University and his team have developed technologies to screen and manipulate the expression of genes in cells. In previous studies, they used these epigenome editing tools to reprogram fibroblasts to become neuronal cells and to control cell differentiation in human neuronal and pluripotent stem cell populations. Interested in exploring a more therapeutic application of these tools, the researchers turned their attention to T cell-based immunotherapies, specifically CAR T cells. According to Gersbach, the use of such epigenetic enhancement approaches on T cells may help expand T cell-based therapies beyond the cancer types, such as blood cancers, in which they have been effective.

By Mariella Bodemeier Loayza Careaga, PhD

Article can be accessed on: The Scientist