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Title of Journal: Cancer Immunol Immunother

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Abbravation: Cancer Immunology, Immunotherapy

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Springer-Verlag

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DOI

10.1016/0377-0273(91)90097-j

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1432-0851

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Comparison of AAV/IL7 autocrine T cell versus p

Authors: ChangXuan You Yong Liu Min Shi Maohua Cao RongCheng Luo Paul L Hermonat
Publish Date: 2009/11/29
Volume: 59, Issue: 5, Pages: 779-787
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Abstract

Adoptive transfer of antigenspecific cytotoxic T lymphocyte CTL into patients holds promise in treating cancer Such anticancer CTL are stimulated by professional antigenpresenting dendritic cells DC We hypothesize the gene delivery of various Th1response cytokines such as interleukin 7 IL7 should further enhance CTL stimulation and activity However the issue as to which cell type DC paracrine or the T cell autocrine should express a particular Th1 cytokine gene for optimal CTL stimulation has never been addressed We used adenoassociated virus2 AAV to compare delivery of IL7 and IL2 genes into DC or T cells and to exogenous commercial cytokines for generating robust carcinoembryonic antigen CEAspecific CTL AAV/IL7 transduction of T cells autocrine delivery generated CTL with the highest killing capability Consistent with this AAV/IL7 delivery generated T cell populations with the highest proliferation highest interferon γ expression highest CD8+CD4+ ratio highest CD8+ CD69+ levels and lowest CD4+ CD25+ Treg levels These data are consistent with higher killing by the AAV/IL7altered CTL These data strongly suggest that IL7 autocrine gene delivery is optimal for CTL generation These data also suggest Th1 cytokine autocrine versus paracrine delivery is an important issue for immunogene therapy and uncovers new questions into cytokine mechanism of action

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