biostudies-literatureMineharu YNINDS NIH HHS827-43https://www.ebi.ac.uk/biostudies/studies/S-EPMC3480576biostudies-literatureUnknown9(4)Immune-mediated gene therapy using adenovirus expressing Flt3 ligand and thymidine kinase followed by ganciclovir administration (Flt3/TK) effectively elicits tumor regression in preclinical glioma models. Herein, we assessed new strategies to optimize Flt3L/TK therapeutic efficacy in a refractory RG2 orthotopic glioblastoma model. Specifically, we aimed to optimize the therapeutic efficacy of Flt3L/TK treatment in the RG2 model by overexpressing the following genes within the brain tumor microenvironment: 1) a TK mutant with enhanced cytotoxicity (SR39 mutant TK), 2) Flt3L-IgG fusion protein that has a longer half-life, 3) CD40L to stimulate DC maturation, 4) T helper cell type 1 polarizing dendritic cell cytokines interleukin-12 or C-X-C motif ligand 10 chemokine (CXCL)-10, 5) C-C motif Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeuticsGene therapy-mediated reprogramming tumor infiltrating T cells using IL-2 and inhibiting NF-κB signaling improves the efficacy of immunotherapy in a brain cancer model.PMC3480576R01 NS061107UO1-NS052465-04S1R01 NS057711F32 NS0581561UO1 NS0524651R01-NS074387U01 NS0524651R01-NS0611071R01-NS0541931R01-NS057711R01 NS0743871F32 NS058156R01 NS054193Puntel MAllison JPMuhammad AKCandolfi MLugo CMineharu YCastro MGXiong WYagiz KLevy EKroeger KMLiu CLowenstein PRKocharian ACurran MAfalseGene therapy-mediated reprogramming tumor infiltrating T cells using IL-2 and inhibiting NF-κB signaling improves the efficacy of immunotherapy in a brain cancer model.Immune-mediated gene therapy using adenovirus expressing Flt3 ligand and thymidine kinase followed by ganciclovir administration (Flt3/TK) effectively elicits tumor regression in preclinical glioma models. Herein, we assessed new strategies to optimize Flt3L/TK therapeutic efficacy in a refractory RG2 orthotopic glioblastoma model. Specifically, we aimed to optimize the therapeutic efficacy of Flt3L/TK treatment in the RG2 model by overexpressing the following genes within the brain tumor microenvironment: 1) a TK mutant with enhanced cytotoxicity (SR39 mutant TK), 2) Flt3L-IgG fusion protein that has a longer half-life, 3) CD40L to stimulate DC maturation, 4) T helper cell type 1 polarizing dendritic cell cytokines interleukin-12 or C-X-C motif ligand 10 chemokine (CXCL)-10, 5) C-C motif 2012-01-01T00:00:00Z2012 Oct2025-07-09T03:04:58.432Z2025-07-09T03:04:58.432ZS-EPMC34805762299623110.1007/s13311-012-0144-7