In vivo retrovirus-mediated herpes simplex virus thymidine kinase gene therapy approach for adult T cell leukemia in a rat model

Ken Murata, Masatoshi Fujita, Yasuaki Yamada, Yoshikazu Higami, Isao Shimokawa, Kunihiro Tsukasaki, Yuetsu Tanaka, Michiyuki Maeda, Koichi Furukawa, Takashi Yoshiki, Hiroshi Shiku, Masao Tomonaga

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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 in vitro, we investigated whether this system could also be effective in vivo, using a rat model. Following infection of the HTLV-I-transformed and tax-expressing rat T cell line TARS-1 with this retrovirus (LNLTK virus), high levels of HSV TK expression were observed and resulted in increased susceptibility to ganciclovir (GCV). Tumors were generated by subcutaneous injection of TARS-1 in newborn syngeneic WKA/H rats. While the tumors derived from infected TARS-1 cells with control virus, as well as uninfected cells, continued to grow in all the rats with 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 elimination of HTLV-I-transformed, tax-expressing T cells in vivo. Therefore, our present study may provide a rationale for clinical gene therapy against adult T cell leukemia.

Original languageEnglish
Pages (from-to)492-500
Number of pages9
JournalJapanese Journal of Cancer Research
Volume88
Issue number5
DOIs
Publication statusPublished - May 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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