MLV/HIV-pseudotyped vectors: a new treatment option for cutaneous T cell lymphomas.
Cutaneous T cell lymphomas (CTCLs) are lymphoproliferative disorders involving the skin. Malignant cells have a CD4+ T-helper phenotype and are found in early stages of the disease in plaques and cutaneous tumors. MLV/HIV-pseudotyped retroviral vectors target gene transfer to CD4-positive T cells and are therefore well suited to be specific delivery vehicles to treat CTCLs. We established a mouse xenograft model for CTCL and generated MLV/HIV-pseudotyped vectors encoding the herpes simplex virus thymidine kinase (HSV-TK), a well-known suicide gene, to prove the efficacy of MLV/HIV vectors in CTCL treatment. Vector particles were intratumorally injected into CTCL nude mouse xenografts. Mice were systemically treated with ganciclovir (GCV) and the tumor tissue was analyzed. A significant delay in tumor growth was observed for HSV-TK-transduced and GCV-treated tumors. GFP expression could be detected exclusively in CD4+ cells of tumors after transduction with GFP-encoding control vectors. The data demonstrate a cell-specific in vivo gene delivery via MLV/HIV-pseudotyped vectors and open new avenues for the treatment of CTCL in humans.
Institute for Biomedical Research, Georg-Speyer Haus, Paul-Ehrlich-Strasse 42-44, D-60596, Frankfurt/Main, Germany.
Sonja
S
Thaler
Angelika M
AM
Burger
Thomas
T
Schulz
Barbara S
BS
Schnierle
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002469:Cell Separation; D005434:Flow Cytometry; D015774:Ganciclovir / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006678:HIV / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009052:Leukemia Virus, Murine / Q000235:genetics*; D008164:Luminescent Proteins / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009368:Neoplasm Transplantation; D010641:Phenotype; D018139:Simplexvirus / Q000201:enzymology; D012878:Skin Neoplasms / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics; D013997:Time Factors
D000998:Antiviral Agents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir