Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells
Ontology highlight
ABSTRACT: The choice of costimulatory domain in CAR design dictates the kinetics of in vivo anti-tumor responses, affecting potency, quality and durability. We show that 1928z results in more vigorous effector functions, whereas 19BBz design compensates for their lesser cytotoxic potency by steadily building up their numbers. Therapeutic function can be further improved by combining CD28 and 4-1BB costimulation. 1928z-41BBL was revealed to provide optimal combined costimulation, exhibiting highly therapeutic efficiency with balanced T cell effector function and accumulation. Endogenous IFN-β/IRF7 pathway activation was found in 1928z-41BBL T cell and is required for effector function acquisition. The role of the IFN-β/IRF7 pathway provides a novel mechanism through which engineering T cells improve therapeutic effect by self-providing ‘signal 3’.
ORGANISM(S): Homo sapiens
PROVIDER: GSE68329 | GEO | 2016/04/19
SECONDARY ACCESSION(S): PRJNA282453
REPOSITORIES: GEO
ACCESS DATA