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.