Figure 3.
Naked plasmid transfer of hFVIII plasmids into hemophilia A mice with or without immunomodulation (costimulation blockade). hFVIII levels and inhibitory antibody formation over time in hemophilia A mice after treatment with pBS-HCRHPI-hFVIIIA beginning on day 1. Transient immunomodulation included Ctla4-Ig on days 1 and 2(n = 8 total; A,B); MR1 on days -1, 1, 2, 7, and 14 (n = 9 total; C,D); and Ctla4-Ig with MR1 (n = 9 total; E,F) using the same combined schedule and dosages as with each individual agent. Fifty μg plasmid in 2 mL saline solution was injected into the tail vein of mice in 5 to 8 seconds. Two separate cohorts of animals (n = 4-5 per group) were used at separate times for each set of immunomodulation experiments; the data from 2 cohorts were combined and presented in the figure. Respective immunosuppressive drugs were administered intraperitoneally at indicated times. #Death of one treated mouse in panel C. Mice were bled at regular intervals. Circulating hFVIII activities and inhibitory antibody titers were evaluated as in Figure 1.

Naked plasmid transfer of hFVIII plasmids into hemophilia A mice with or without immunomodulation (costimulation blockade). hFVIII levels and inhibitory antibody formation over time in hemophilia A mice after treatment with pBS-HCRHPI-hFVIIIA beginning on day 1. Transient immunomodulation included Ctla4-Ig on days 1 and 2(n = 8 total; A,B); MR1 on days -1, 1, 2, 7, and 14 (n = 9 total; C,D); and Ctla4-Ig with MR1 (n = 9 total; E,F) using the same combined schedule and dosages as with each individual agent. Fifty μg plasmid in 2 mL saline solution was injected into the tail vein of mice in 5 to 8 seconds. Two separate cohorts of animals (n = 4-5 per group) were used at separate times for each set of immunomodulation experiments; the data from 2 cohorts were combined and presented in the figure. Respective immunosuppressive drugs were administered intraperitoneally at indicated times. #Death of one treated mouse in panel C. Mice were bled at regular intervals. Circulating hFVIII activities and inhibitory antibody titers were evaluated as in Figure 1.

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