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Selective inhibition of human T-lymphotropic virus type I-transformed human T-cell growth by a tax-targeted conditionally cytotoxic recombinant retrovirus

M Fujita, K Murata and H Shiku

Department of Oncology, Nagasaki University School of Medicine, Japan.

Adult T-cell leukemia (ATL), a disorder associated with high mortality rates, arises from human T-lymphotropic virus type I (HTLV-I)-infected CD4+ T cells. We designed a retroviral vector-based gene therapy approach to ATL. The long terminal repeat (LTR) of HTLV-I is transactivated by the viral tax protein. We constructed a hybrid gene consisting of herpes simplex virus thymidine kinase (HSV TK) under the control of the HTLV-I LTR and inserted it into a retroviral vector. When HTLV-I-transformed and tax-expressing human T-cell lines were infected with this recombinant retrovirus (LNLTK alpha virus), they expressed high levels of HSV TK and exhibited increased sensitivity to acyclovir, a nucleoside analog that is converted to the toxic anabolite after phosphorylation by the HSV TK. On the other hand, the retroviral infection had little effect on acyclovir-induced cytotoxicity in HTLV-I- negative human hematopoietic cell lines. Our data may provide the prospect of the gene therapy for ATL by tax-targeted selective elimination of leukemic cells.

Volume 84, Issue 8, pp. 2591-2596, 10/15/1994
Copyright © 1994 by The American Society of Hematology


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