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Volume 14, Issue 1, Pages (July 2006)

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Presentation on theme: "Volume 14, Issue 1, Pages (July 2006)"— Presentation transcript:

1 Volume 14, Issue 1, Pages 107-117 (July 2006)
A Phase I Trial of Intravenous CG7870, a Replication-Selective, Prostate-Specific Antigen–Targeted Oncolytic Adenovirus, for the Treatment of Hormone-Refractory, Metastatic Prostate Cancer  Eric J. Small, Michael A. Carducci, James M. Burke, Ron Rodriguez, Lawrence Fong, Lynn van Ummersen, D.C. Yu, Junko Aimi, Dale Ando, Peter Working, David Kirn, George Wilding  Molecular Therapy  Volume 14, Issue 1, Pages (July 2006) DOI: /j.ymthe Copyright © 2006 The American Society of Gene Therapy Terms and Conditions

2 FIG. 1 Representative laboratory data on the two patients treated with the highest dose of CG7870 (6 × 1012 vp). (A) d-dimer; (B) prothrombin time (PT), partial thromboplastin time (PTT); (C) aspartate transaminase, alanine transaminase; (D) platelets; (E) lymphocytes. Molecular Therapy  , DOI: ( /j.ymthe ) Copyright © 2006 The American Society of Gene Therapy Terms and Conditions

3 FIG. 2 CG7870 genome positivity over time following CG7870 intravenous infusion. The percentage of patients in each of the three dose ranges is shown, with detectable genomes in plasma at each of the time points following intravenous infusion of the virus: (A–C) low (1010, 3 × 1010, 1011), white bar; (D–F) intermediate (3 × 1011, 6 × 1011, 1012), black bar; (G, H) high (3 × 1012 and 6 × 1012), gray bar. Molecular Therapy  , DOI: ( /j.ymthe ) Copyright © 2006 The American Society of Gene Therapy Terms and Conditions

4 FIG. 3 Acute cytokine induction following CG7870 intravenous (IV) infusion. Concentrations of interleukin 6 (IL-6; pg/ml) 6 hours after IV infusion of the virus are represented for each patient per dose cohort (dose levels shown on x-axis); concentrations shown on log scale on y-axis (A). IL-6 concentrations peaked at 6 hours after dosing. Concentrations of interleukin-10 (IL-10; pg/ml) 12–24 hours after IV infusion of the virus are represented for each patient per dose cohort (dose levels shown on x-axis); concentrations shown on linear scale on y-axis (B). IL-10 concentrations peaked between 12 and 24 hours after dosing. Molecular Therapy  , DOI: ( /j.ymthe ) Copyright © 2006 The American Society of Gene Therapy Terms and Conditions

5 FIG. 4 Dose-related decreases in diastolic and systolic blood pressure after CG7870 dosing. The maximum percentage change in patient blood pressure from baseline to 8–12 hours after treatment is represented for each patient in gray bars (diastolic top panel; systolic, lower panel). The mean change for each dose group is represented by the black bar (absolute number for mean change shown). Bars directed upward (above the zero line) represent an increase in blood pressure, whereas a bar directed downward represents a decrease in blood pressure. Molecular Therapy  , DOI: ( /j.ymthe ) Copyright © 2006 The American Society of Gene Therapy Terms and Conditions

6 FIG. 5 CG7870 genetic construct. PB, rat probasin promoter (controls expression of E1A); PSE, prostate-specific element promoter-enhancer region (controlling expression of E1B region genes). ITR, inverted terminal repeat region of Ad5. Molecular Therapy  , DOI: ( /j.ymthe ) Copyright © 2006 The American Society of Gene Therapy Terms and Conditions


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