TY - JOUR
T1 - Characterisation of systemic dissemination of nonreplicating adenoviral vectors from tumours in local gene delivery
AU - Wang, Y.
AU - Yang, Z.
AU - Liu, S.
AU - Kon, T.
AU - Krol, A.
AU - Li, C. Y.
AU - Yuan, F.
N1 - Funding Information:
We thank Drs David Zaharoff and Sheng Tong for the scientific discussion, and Drs Jun Chen and Lori Setton for the help in PCR experiment. This work is supported in part by grants from the National Science Foundation (BES-9984062) and the National Institutes of Health (CA81512).
PY - 2005/4/25
Y1 - 2005/4/25
N2 - Systemic virus dissemination is a potential problem during local gene delivery in solid tumours. However, the kinetics and pathways of the dissemination have not been well characterised during the first 24 h after the infusion is started. To this end, we infused adenoviral vectors for luciferase or enhanced green fluorescence protein into three different tumour models in mice. During and/or after the infusion, we determined the amount of adenoviruses in the tumour, blood, and liver, and examined the transgene expression in the liver, lung, blood, and tumour. In addition, we intravenously injected tumour cells expressing luciferase and examined the biodistribution of these cells in the body. We observed transgene expression in the liver and tumour at 24 h after the infusion, but could not detect transgene expression in the blood and lung. The peak concentration of viral vectors in the plasma occurred during the intratumoral infusion. At 10 min after the infusion, few viral vectors remained in the blood and the ratio of copy numbers of adenoviruses between liver and tumour was > 2 in 80% and ≥ 10 in 40% of the mice. Most tumour cells injected intravenously accumulated in the lung within the first 24 h. Taken together, these data indicated that systemic virus dissemination occurred mainly during the first 10 min after the intratumoral infusion was started, and that the dissemination was due to infusion-induced convective transport of viral vectors into leaky tumour microvessels.
AB - Systemic virus dissemination is a potential problem during local gene delivery in solid tumours. However, the kinetics and pathways of the dissemination have not been well characterised during the first 24 h after the infusion is started. To this end, we infused adenoviral vectors for luciferase or enhanced green fluorescence protein into three different tumour models in mice. During and/or after the infusion, we determined the amount of adenoviruses in the tumour, blood, and liver, and examined the transgene expression in the liver, lung, blood, and tumour. In addition, we intravenously injected tumour cells expressing luciferase and examined the biodistribution of these cells in the body. We observed transgene expression in the liver and tumour at 24 h after the infusion, but could not detect transgene expression in the blood and lung. The peak concentration of viral vectors in the plasma occurred during the intratumoral infusion. At 10 min after the infusion, few viral vectors remained in the blood and the ratio of copy numbers of adenoviruses between liver and tumour was > 2 in 80% and ≥ 10 in 40% of the mice. Most tumour cells injected intravenously accumulated in the lung within the first 24 h. Taken together, these data indicated that systemic virus dissemination occurred mainly during the first 10 min after the intratumoral infusion was started, and that the dissemination was due to infusion-induced convective transport of viral vectors into leaky tumour microvessels.
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U2 - 10.1038/sj.bjc.6602494
DO - 10.1038/sj.bjc.6602494
M3 - Article
C2 - 15812558
AN - SCOPUS:18944387569
SN - 0007-0920
VL - 92
SP - 1414
EP - 1420
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 8
ER -