Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of our study was to examine the potential usefulness of transducing the protein kinase C-gamma (PKC-gamma) cDNA gene into tumor-specific T cells as a technique for facilitating the generation of large numbers of functional Ag-specific T for tumor therapy. Murine CD8+, F-MuLV gag-specific CTL clones, and CD4+, F-MuLV env-specific Th clones, as well as bulk-cultured T cell lines with defined Ag specificity to FBL-3, a Friend murine leukemia virus (F-MuLV)-induced tumor, were transduced with a retroviral vector pZipNeoPKC-gamma and selected in G418. The results demonstrated that PKC-gamma-transduced clones remained activated in culture, as evidenced by continued expression of up-regulated levels of IL-2R, which were as high after 6 mo in culture without Ag restimulation as 24 h after Ag stimulation. In vitro functional studies demonstrated that PKC-gamma-transduced CD8+ T cell clones maintained specific cytolytic activity to FBL-3, and PKC-gamma-transduced CD4+ T cell clones maintained specific proliferative activity to FBL-3 or F-MuLV Ag presented by irradiated syngeneic APC. Short-term bulk-cultured T cells specific to FBL-3 were also transduced and could be grown long term in vitro with maintenance of functional specificity. In vivo study showed that PKC-gamma-transduced CD4+ T cells were able to proliferate in response to Ag plus IL-2 stimulation in vivo in a similar pattern as the parental T cells. Therapy with adoptively transferred PKC-gamma-transduced T cell clones and lines into syngeneic mice, with or without FBL-3 tumor, showed that the PKC-gamma-transduced T cells were not tumorigenic and were effective in curing mice with disseminated FBL-3.
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PMID:Retroviral transduction of protein kinase C-gamma into tumor-specific T cells allows antigen-independent long-term growth in IL-2 with retention of functional specificity in vitro and ability to mediate tumor therapy in vivo. 793 May 83