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• W2085723131 abstract "In Brief Adoptive transfer of antigen-specific CD8+ T cells can effectively treat patients with metastatic melanoma. Recent efforts have emphasized the in vitro generation of antitumor T cells by transduction of genes encoding antitumor T-cell receptors. At present, lentiviral vector-mediated transduction of CD8+ T cells relies on anti-CD3/CD28 bead stimulation; however, this method fails to efficiently expand CD8+ T cells. Herein we sought to establish a methodology for lentiviral vector transduction using optimal activating agents for efficient gene delivery and robust expansion of CD8+ T cells. To overcome the inability of anti-CD3/CD28 beads to efficiently expand CD8+ T cells, we evaluated alternative activating agents including feeder cells from allogeneic peripheral blood mononuclear cells and plate-bound anti-CD3 antibody. Analyses of gene transfer, cell phenotype, fold expansion, and biologic activities were used to determine the optimal methodology. Plate-bound anti-CD3 provided an ideal activation platform that afforded optimal lentiviral vector-mediated gene transfer efficiency (up to 90%), and coupled with peripheral blood mononuclear cells feeder cells yielded up to 600-fold expansion of CD8+ T cells within 12 days. The T-cell antigen receptor (TCR) engineered CD8+ T cells conferred specific antitumor activity and many displayed a central memory-like phenotype. The methodology described here could be readily applied for engineering CD8+ T cells with antitumor specificity for human adoptive immunotherapy. Supplemental Digital Content is available in the article" @default.
• W2085723131 created "2016-06-24" @default.
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• W2085723131 date "2010-07-01" @default.
• W2085723131 modified "2023-09-24" @default.
• W2085723131 title "A Simplified Method for the Clinical-scale Generation of Central Memory-like CD8+ T Cells After Transduction With Lentiviral Vectors Encoding Antitumor Antigen T-cell Receptors" @default.
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• W2085723131 doi "https://doi.org/10.1097/cji.0b013e3181e311cb" @default.
• W2085723131 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7365020" @default.
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