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- W198401270 abstract "Abstract Adoptive immunotherapy is a promising new treatment modality for patients with advanced malignancies. A key limitation to adoptive T cell transfer is generating sufficient numbers of tumor reactive T cells for patient treatment. We have developed the ability to engineer T cells with TCR genes to redirect the specificity of PBL-derived T cells. A novel population we can produce are MHC class I restricted CD4+ T cells. CD4+ T cells have been implicated in the priming and maintenance of the CD8+ T cell response, in addition to having cytolytic properties in experimental models. In this study, tyrosinase-reactive human CD4+ T cells were created by retroviral transduction using a CD8-independent T cell receptor. Tyrosinase-reactive gene-modifed CD4+ cells produced IFN-γ, GM-CSF, and IL-2 in an HLA-A2 restricted, antigen-specific manner. Following tumor antigen recognition in vitro, TCR-transduced CD4+ T cells upregulated secondary costimulatory molecules, including OX-40 and 4-1BB. Despite their type I phenotype, priming of CD8+ cells by MART-1-loaded dendritic cells was impaired by these TCR-transduced CD4+ cells. Therefore, simultaneous engraftment of genetically-engineered CD4+ and CD8+ effector T cells may inhibit tumor killing by suppressing both CD8+ T cell induction and maintenance." @default.
- W198401270 created "2016-06-24" @default.
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- W198401270 date "2011-04-01" @default.
- W198401270 modified "2023-09-23" @default.
- W198401270 title "TCR transduced CD4+ T cells exhibit a TH1 phenotype while inhibiting priming of naïve CD8+ T cells by peptide-loaded mature dendritic cells (48.19)" @default.
- W198401270 doi "https://doi.org/10.4049/jimmunol.186.supp.48.19" @default.
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