Bone marrow-derived, endothelial progenitor-like cells as angiogenesis-selective gene-targeting vectors.
Human and mouse proliferation-competent, bone marrow or peripheral circulation derived endothelial progenitor-like cells (EPCs) were isolated, expanded and genetically engineered ex vivo to express the beta galactosidase (beta-gal), green fluorescence protein or thymidine kinase (TK) genes using retrovirus-mediated gene transfer. Genetically labeled EPCs were transplanted into sublethally irradiated tumor-bearing mice and were found to migrate to and incorporate into the angiogenic vasculature of growing tumors while maintaining transgene expression. Ganciclovir treatment resulted in significant tumor necrosis in animals previously administered TK-expressing EPCs with no systemic toxicity. These results demonstrate the feasibility of using genetically modified EPCs as angiogenesis-selective gene-targeting vectors and the potential of this approach to mediate non-toxic and systemic antitumor responses.
Ferrari
N
N
Neuro-Oncology Branch, National Cancer Institute, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Glod
J
J
Lee
J
J
Kobiler
D
D
Fine
H A
HA
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D000998:Antiviral Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology; D015774:Ganciclovir / Q000627:therapeutic use; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D051379:Mice; D008817:Mice, Mutant Strains; D009369:Neoplasms / Q000628:therapy*; D009389:Neovascularization, Pathologic; D013937:Thymidine Kinase / Q000235:genetics
D018952:Antigens, CD34; D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir