AUTHOR=Hombach Andreas A., Abken Hinrich 

TITLE=Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle

JOURNAL=Frontiers in Immunology

VOLUME=Volume 4 - 2013

YEAR=2013

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2013.00135

DOI=10.3389/fimmu.2013.00135

ISSN=1664-3224

ABSTRACT=Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukaemia 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 KLRG-1+ 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-tumour response and to improve the over-all efficacy of adoptive cell therapy.