FOXO1 is a master regulator of memory programming in CAR T cells
Stanford University · Children's Hospital of Philadelphia · +4 more institutions
Abstract
Abstract A major limitation of chimeric antigen receptor (CAR) T cell therapies is the poor persistence of these cells in vivo 1 . The expression of memory-associated genes in CAR T cells is linked to their long-term persistence in patients and clinical efficacy 2–6 , suggesting that memory programs may underpin durable CAR T cell function. Here we show that the transcription factor FOXO1 is responsible for promoting memory and restraining exhaustion in human CAR T cells. Pharmacological inhibition or gene editing of endogenous FOXO1 diminished the expression of memory-associated genes, promoted an exhaustion-like phenotype and impaired the antitumour activity of CAR T cells. Overexpression of FOXO1 induced a…
Citation impact
- FWCI
- 45.37
- Percentile
- 100%
- References
- 61
Authors
34- ADAlexander DoanCorresponding
Stanford University
- KPKatherine P. Mueller
Children's Hospital of Philadelphia, University of Pennsylvania
- AYAndy Y. Chen
Gladstone Institutes, Stanford University
- GTGeoffrey T. Rouin
Children's Hospital of Philadelphia, University of Pennsylvania
- YCYingshi Chen
Children's Hospital of Philadelphia, University of Pennsylvania
Topics & keywords
- Chimeric antigen receptor
- Regulator
- FOXO1
- Master regulator
- Cell biology
- Persistence (discontinuity)
- Antigen
- In vivo