Overcoming intrinsic inhibitory pathways to augment the antineoplastic activity of adoptively transferred T cells: Re-tuning your CAR before hitting a rocky road.
Effector T cells become rapidly inactivated after antigen exposure due to extracellular as well as intrinsic signals. We have recently demonstrated that the deletion of diacylglycerol kinases, intrinsic inhibitors of T-cell signaling, enhances the activity of adoptively transferred T cells expressing a chimeric antigen receptor (CAR) specific for a tumor-associated antigen.
Thoracic Oncology Research Laboratory; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
Liang-Chuan S
LC
Wang
Division of Hematology/Oncology; Department of Medicine; Medical College of Wisconsin; Blood Research Institute; Blood Center of Wisconsin; Milwaukee, WI USA.
Matthew J
MJ
Riese
Thoracic Oncology Research Laboratory; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
Edmund K
EK
Moon
Thoracic Oncology Research Laboratory; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
Steven M
SM
Albelda
Chimeric Antigen Receptor; T cell hypofunction; diacylglycerol kinase; tumor immunosuppression; tumor microenvironment