February 6, 2017 (The Journal of Clinical Investigation)
Part of the reason why treatment of solid tumors using CAR T-cells has been troublesome is because of adenosine production. Production of adenosine is part of the tumor-induced immunosuppressive mechanism. Adenosine, which is produced by tumor cells, prevents antitumor T cell responses.
In a recent study, published in The Journal of Clinical Investigation, researchers investigated whether targeting adensoine-mediated immunosuppression might enhance CAR T Cell efficacy. They demonstrated that “CAR T cells upregulate A2ARs upon antigen-specific stimulation in vitro and in vivo.” This translates that the A2AR-deficient CAR T cells had significantly greater efficacy than WT CART cells (the control).
The conclusion is that A2AR targeting used in combination with engineered CAR T cells and a checkpoint blockade may significantly increase the efficacy of CAR T therapy.
Read more about this research at The Journal of Clinical Investigation.
