Normals

The early Ad gene therapy trials demonstrated that, although effective gene transfer could be achieved, persistence of expression is clearly a problem for Ad vectors. There was

Figure 7 Time course of gene expression and anatomical response after administration of Ad expressing vascular endothelial growth factor (VEGF). The retroperitoneal fat pad of rats was injected with 5 X 108 pfu of either AdVEGF (a first-generation E1 ~E3~ vector expressing the 165 amino acid form of human VEGF, solid symbols) or the control vector expressing no transgene (AdNull, open symbols). At intervals, animals were anesthetized, a laporatomy performed, and the fat pad photographed. The number of vessels crossing a circle of 1 cm diameter centered on the injection site were measured (left axis - □, ■). The fat pad was also homogenized and the level of VEGF determined by enzyme-linked immunosorbent assay [right axis - o, •; (160)].

Figure 7 Time course of gene expression and anatomical response after administration of Ad expressing vascular endothelial growth factor (VEGF). The retroperitoneal fat pad of rats was injected with 5 X 108 pfu of either AdVEGF (a first-generation E1 ~E3~ vector expressing the 165 amino acid form of human VEGF, solid symbols) or the control vector expressing no transgene (AdNull, open symbols). At intervals, animals were anesthetized, a laporatomy performed, and the fat pad photographed. The number of vessels crossing a circle of 1 cm diameter centered on the injection site were measured (left axis - □, ■). The fat pad was also homogenized and the level of VEGF determined by enzyme-linked immunosorbent assay [right axis - o, •; (160)].

clearly an immune response to the vector and possibly the transgene itself; however, the biology of that response is not well understood. Animal models, particularly those involving inbred mice, have limited utility in predicting the immune response in humans. To assess the human host response to Ad vectors, 2 trials with normal subjects have been performed using intradermal (144) or intratracheal administration of an Ad vector expressing the E. coli CD gene. The intent of these trials is to describe the immune response in humans to an El E3 " Ad vector to provide a background to assess more advanced vectors on a rational basis.

Was this article helpful?

0 0

Post a comment