Neuroblastoma killing properties of V?2 and V?2-negative ??T cells following expansion by artificial antigen-presenting cells.

ABSTRACT: PURPOSE:The majority of circulating human ??T lymphocytes are of the V?9V?2 lineage, and have T-cell receptor (TCR) specificity for nonpeptide phosphoantigens. Previous attempts to stimulate and expand these cells have therefore focused on stimulation using ligands of the V?9V?2 receptor, whereas relatively little is known about variant blood ??T subsets and their potential role in cancer immunotherapy. EXPERIMENTAL DESIGN:To expand the full repertoire of ??T without bias toward specific TCRs, we made use of artificial antigen-presenting cells loaded with an anti ??TCR antibody that promoted unbiased expansion of the ??T repertoire. Expanded cells from adult blood donors were sorted into 3 populations expressing respectively V?2 TCR chains (V?2(+)), V?1 chains (V?1(+)), and TCR of other ? chain subtypes (V?1(neg)V?2(neg)). RESULTS:Both freshly isolated and expanded cells showed heterogeneity of differentiation markers, with a less differentiated phenotype in the V?1 and V?1(neg)V?2(neg) populations. Expanded cells were largely of an effector memory phenotype, although there were higher numbers of less differentiated cells in the V?1(+) and V?1(neg)V?2(neg) populations. Using neuroblastoma tumor cells and the anti-GD2 therapeutic mAb ch14.18 as a model system, all three populations showed clinically relevant cytotoxicity. Although killing by expanded V?2 cells was predominantly antibody dependent and proportionate to upregulated CD16, V?1 cells killed by antibody-independent mechanisms. CONCLUSIONS:In conclusion, we have demonstrated that polyclonal-expanded populations of ??T cells are capable of both antibody-dependent and -independent effector functions in neuroblastoma.

SUBMITTER: Fisher JP 

PROVIDER: S-EPMC4445920 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature