IN-VIVO RETROVIRUS-MEDIATED HERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE-THERAPY APPROACH FOR ADULT T-CELL LEUKEMIA IN A RAT MODEL

We have previously demonstrated that human T-lymphotropic virus type I (HTLV-I) tax-expressing human T cell lines are selectively eliminated in the presence of aciclovir, using a retroviral vector carrying the herpes simplex virus thymidine kinase (HSV TK) gene under the control of the long terminal repeat (LTR) of HTLV-I, Based on these findings i n vitro, we investigated whether this system could also be effective i n vivo, using a rat model, Following infection of the HTLV-I-transform ed and tax-expressing rat T cell line TARS-1 with this retrovirus (LNL TK virus), high levels of HSV TK expression were observed and resulted in increased susceptibility to ganciclovir (GCV), Tumors were generat ed by subcutaneous injection of TARS-1 in newborn syngeneic WKA/H rats , While the tumors derived from infected TARS-1 cells with control vir us, as well as uninfected cells, continued to grow in all the rats wit h or without administration of GCV, those derived from LNLTK-infected cells exhibited dramatic regression upon GCV treatment, These results indicate that the HTLV-I LTR-HSV TK system also causes selective elimi nation of HTLV-I-transformed, tax-expressing T cells in vivo, Therefor e, our present study may provide a rationale for clinical gene therapy against adult T cell leukemia.