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MLV/HIV-pseudotyped vectors: a new treatment option for cutaneous T cell lymphomas.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2003 Nov; Vol. 8 (5), pp. 756-61. - Publication Year :
- 2003
-
Abstract
- 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.
- Subjects :
- Animals
Antiviral Agents therapeutic use
CD4-Positive T-Lymphocytes metabolism
Cell Line
Cell Line, Tumor
Cell Separation
Flow Cytometry
Ganciclovir therapeutic use
Green Fluorescent Proteins
Humans
Immunohistochemistry
Luminescent Proteins metabolism
Mice
Mice, Nude
NIH 3T3 Cells
Neoplasm Transplantation
Phenotype
Simplexvirus enzymology
Thymidine Kinase genetics
Time Factors
Gene Transfer Techniques
Genetic Therapy methods
Genetic Vectors
HIV genetics
Leukemia Virus, Murine genetics
Lymphoma, T-Cell, Cutaneous therapy
Skin Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0016
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 14599808
- Full Text :
- https://doi.org/10.1016/s1525-0016(03)00241-7