Use of blood outgrowth endothelial cells as virus-producing vectors for gene delivery to tumors.
Cell-based delivery of therapeutic viruses has potential advantages over systemic viral administration, including attenuated neutralization and improved viral targeting. One of the exciting new areas of investigation is the potential ability of endothelial-lineage cells to deliver genes to the areas of neovascularization. In the present study, we compared two types of endothelial-lineage cells [outgrowth endothelial cells (OECs) and culture-modified mononuclear cells (CMMCs), also known as "endothelial progenitor cells"] for their ability to be infected with adenovirus and to home to the areas of neovascularization. Both cell types were isolated from peripheral blood of healthy human donors and expanded in culture. We demonstrate that OECs are more infectable and home better to tumors expressing VEGF on systemic administration. Furthermore, we used an adenoviral/retroviral chimeric system to convert OECs to retrovirus-producing cells. When injected systemically into tumor-bearing mice, OECs retain their ability to produce retrovirus and infect surrounding tumor cells. Our data demonstrate that OECs could be efficient carriers for viral delivery to areas of tumor neovascularization.
Jevremovic
Dragan
D
Division of Pathology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Gulati
Rajiv
R
Hennig
Ivo
I
Diaz
Rosa Maria
RM
Cole
Caroline
C
Kleppe
Laurel
L
Cosset
Francois Loic
FL
Simari
Robert D
RD
Vile
Richard G
RG
D000256:Adenoviridae / Q000235:genetics*; D000257:Adenoviridae Infections / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D002678:Chimera; D004730:Endothelium, Vascular / Q000166:cytology* / Q000821:virology*; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009000:Monocytes / Q000166:cytology / Q000821:virology; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000821:virology; D009389:Neovascularization, Pathologic; D012190:Retroviridae / Q000235:genetics*; D012192:Retroviridae Infections / Q000235:genetics