A non-human primate model for analysis of safety, persistence, and function of adoptively transferred T cells

Abstract

Background Adoptive immunotherapy with antigen-specific effector T-cell (TE) clones is often limited by poor survival of the transferred cells. We describe here a Macaca nemestrina model for studying transfer of T-cell immunity. Methods We derived, expanded, and genetically marked CMV-specific CD8+ TE clones with surface markers expressed on B cells. TE cells were adoptively transferred, and toxicity, persistence, retention of introduced cell-surface markers, and phenotype of the persisting T cells were evaluated. Results CD8+ TE clones were efficiently isolated from distinct memory precursors and gene-marking with CD19 or CD20 permitted in vivo tracking by quantitative PCR. CD19 was a more stable surface marker for tracking cells in vivo and was used to re-isolate cells for functional analysis. Clonally derived CD8+ TE cells differentiated in vivo to phenotypically and functionally heterogeneous memory T-cell subsets. Conclusions These studies demonstrate the utility of Macaca nemestrina for establishing principles for T-cell therapeutics applicable to humans. © 2010 John Wiley & Sons A/S.