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Young T cells age during a redirected anti-tumour attack: chimeric antigen receptor (CAR)-provided dual costimulation is half the battle.

By Andreas A Hombach and Hinrich eAbken

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

Topics: OX40, CD28, memory T cells, CCR7, Chimeric Antigen Receptor, adoptive cell therapy, Immunologic diseases. Allergy, RC581-607
Publisher: Frontiers Media S.A.
Year: 2013
DOI identifier: 10.3389/fimmu.2013.00135
OAI identifier: oai:doaj.org/article:135cad35243e4567a6edd2ea2529e500
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