The CD3-Zeta Chimeric Antigen Receptor Overcomes TCR Hypo-Responsiveness of Human Terminal Late-Stage T Cells
作者： Gunter Rappl , Tobias Riet , Sabine Awerkiew , Annette Schmidt , Andreas A. Hombach
DOI: 10.1371/JOURNAL.PONE.0030713
关键词:
摘要: Adoptive therapy of malignant diseases with tumor-specific cytotoxic T cells showed remarkable efficacy in recent trials. Repetitive cell receptor (TCR) engagement target antigen, however, inevitably ends up hypo-responsive terminally differentiated KLRG-1+ CD57+ CD7− phenotype limiting their therapeutic efficacy. We here revealed that hypo-responsiveness CMV-specific late-stage CD8+ is due to reduced TCR synapse formation compared younger cells. Membrane anchoring components contributes since dislocation galectin-3 from the by swainsonine restored both and response. Transgenic expression a CD3-zeta signaling chimeric antigen (CAR) recovered full effector functions indicating defect restricted membrane while transgenic CAR was not blocked. engineered released cytokines mediated redirected cytotoxicity as efficiently Our data provide rationale for independent, activation adoptive avoid upon repetitive encounter.
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