title: Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle.
abstract: Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient's T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1(+) CD57(+) CD7(-) CCR7(-) phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy.
authors.affiliation: Center for Molecular Medicine Cologne, University of Cologne , Cologne , Germany ; Department I Internal Medicine, University Hospital Cologne , Cologne , Germany.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Hombach
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
keywords: CD28; OX40; adoptive cell therapy; chimeric antigen receptor; memory T cells