title: Combined cytolytic effects of a vaccinia virus encoding a single chain trimer of MHC-I with a Tax-epitope and Tax-specific CTLs on HTLV-I-infected cells in a rat model.
abstract: Adult T cell leukemia (ATL) is a malignant lymphoproliferative disease caused by human T cell leukemia virus type I (HTLV-I). To develop an effective therapy against the disease, we have examined the oncolytic ability of an attenuated vaccinia virus (VV), LC16m8Δ (m8Δ), and an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) line, 4O1/C8, against an HTLV-I-infected rat T cell line, FPM1. Our results demonstrated that m8Δ was able to replicate in and lyse tumorigenic FPM1 cells but was incompetent to injure 4O1/C8 cells, suggesting the preferential cytolytic activity toward tumor cells. To further enhance the cytolysis of HTLV-I-infected cells, we modified m8Δ and obtained m8Δ/RT1AlSCTax180L, which can express a single chain trimer (SCT) of rat major histocompatibility complex class I with a Tax-epitope. Combined treatment with m8Δ/RT1AlSCTax180L and 4O1/C8 increased the cytolysis of FPM1V.EFGFP/8R cells, a CTL-resistant subclone of FPM1, compared with that using 4O1/C8 and m8Δ presenting an unrelated peptide, suggesting that the activation of 4O1/C8 by m8Δ/RT1AlSCTax180L further enhanced the killing of the tumorigenic HTLV-I-infected cells. Our results indicate that combined therapy of oncolytic VVs with SCTs and HTLV-I-specific CTLs may be effective for eradication of HTLV-I-infected cells, which evade from CTL lysis and potentially develop ATL.
authors.affiliation: Division of Molecular Virology, Institute for Genetic Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Takashi
authors.identifier: 0000-0002-3769-4224
authors.initials: T
authors.lastname: Ohashi
authors.affiliation: Division of Integrative Bioscience, Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Tottori 683-8503, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Virology III, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kidokoro
authors.affiliation: Division of Molecular Virology, Institute for Genetic Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Molecular Virology, Institute for Genetic Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Shida
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016355:Genes, pX / Q000235:genetics*; D015490:HTLV-I Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D007371:Interferon-gamma