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Cytosine deaminase/5‐fluorocytosine gene therapy can induce efficient anti‐tumor effects and protective immunity in immunocompetent mice but not in athymic nude mice
Author(s) -
Kuriyama, Shigeki,
Kikukawa Masaji,
Masui Kazuhiro,
Okuda Hirotsugu,
Nakatani Toshiya,
Sakamoto Takemi,
Yoshiji Hitoshi,
Fukui Hiroshi,
Ikenaka Kazuhiro,
Mullen Craig A.,
Tsujii Tadasu
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990517)81:4<592::aid-ijc15>3.0.co;2-i
Subject(s) - cytosine deaminase , immunity , genetic enhancement , immunology , ratón , cancer research , gene , adenosine deaminase , biology , medicine , immune system , virology , genetics , enzyme , biochemistry
Murine hepatocellular carcinoma cells were retrovirally transduced with the bacterial cytosine deaminase ( CD ) gene. CD ‐transduced cells exhibited more than 120‐fold higher sensitivity to 5‐fluorocytosine (5‐FC) compared with parental cells. When syngeneic immunocompetent mice were inoculated s.c. with parental hepatocellular carcinoma cells containing as little as 5% CD ‐transduced cells, significant inhibition of tumor formation was induced by 5‐FC treatment. Furthermore, established solid tumors in immunocompetent mice containing only 5% CD ‐transduced cells were infiltrated markedly with CD4 + and CD8 + T lymphocytes and macrophages by 5‐FC treatment, such that significant reduction or even complete regression of tumors was observed. These tumor‐free mice resisted subsequent rechallenge with wild‐type tumor. Conversely, when athymic nude mice were inoculated with a cell mixture containing CD ‐transduced cells and parental cells at a ratio of 40:60, all developed tumors despite 5‐FC treatment. Our results indicate that gene therapy using the CD /5‐FC system can induce efficient anti‐tumor effects and protective immunity in immunocompetent mice but not in athymic immunodeficient mice, suggesting that the host's immunocompetence may be a critical factor for achieving successful gene therapy against cancer. Int. J. Cancer 81:592–597, 1999. © 1999 Wiley‐Liss, Inc.