Publications by authors named "Janette Mata-Alcazar"
Article Synopsis
- Adenosine (Ado) plays a role in suppressing immune responses in tumors, and exhausted CD8 CAR-T cells express enzymes CD39 and CD73 that contribute to Ado production.
- Researchers attempted to improve CAR-T cell effectiveness by knocking out these enzymes or an adenosine receptor, but saw only minor improvements.
- However, overexpressing adenosine deaminase (ADA-OE) to convert Ado to inosine (INO) notably enhanced CAR-T cell function, stemness, and metabolic reprogramming, leading to superior CAR-T products suitable for clinical use.
Adenosine (Ado) mediates immune suppression in the tumor microenvironment and exhausted CD8 CAR T cells mediate Ado-induced immunosuppression through CD39/73-dependent Ado production. Knockout of CD39, CD73 or A2aR had modest effects on exhausted CAR T cells, whereas overexpression of Ado deaminase (ADA), which metabolizes Ado to inosine (INO), induced stemness features and potently enhanced functionality. Similarly, and to a greater extent, exposure of CAR T cells to INO augmented CAR T cell function and induced hallmark features of T cell stemness.
View Article and Find Full Text PDF