Fig 1. Integrating lentiviral vectors induce greater IL12 expression, leading to superior control in multiple syngeneic tumor models.

(A, B) CD11c+ HLA-DR+ DC-SIGN+ human dendritic cells were transduced with integrating lentiviral vector (ILV) or non-integrating lentiviral vector (NILV) expressing GFP for 72 hours. (p < 0.0001, representative data from 3 independent experiments). (C, D) Mice were injected with ILVs or NILVs expressing firefly luciferase (1 x 10¹⁰ vector genomes) subcutaneously at the base of the tail on Day 0. Luciferase expression was monitored over 28 days (*p = 0.006, **p < 0.0001 representative data from 3 independent experiments). (E, F) Mice inoculated with B16F10 syngeneic melanoma tumors in their flanks were treated with a single shot of NILVs or ILVs expressing mouse IL12 on Day 0. Whole blood was collected from mice weekly until 21 days post-immunization and serum was analyzed for IL12p70 (*p = 0.02) and IFNγ (*p = 0.004, **p = 0.0005, ***p < 0.0001, representative data from 3 independent studies). (G) Mice were inoculated subcutaneously with colon carcinoma (CT26, n = 9), B cell lymphoma (A20, n = 9), melanoma (B16, n = 3–8) or mastocytoma (P815, n = 5) or orthotopically with mammary carcinoma (4T1, n = 9), then treated with a single shot of either ILV expressing mIL-12 or NILV expressing mIL-12 when tumors were palpable (Day 7–10). Graphs represent tumor growth of individual mice in each treatment group. Data points and error bars in (A-F) represent mean and standard error of the mean for representative studies, respectively. Statistical significance was determine using one-way ANOVA analysis followed by Tukey multiple comparison tests and p < 0.05 was considered significant.