title: Autologous Tax-specific CTL therapy in a primary adult T cell leukemia/lymphoma cell-bearing NOD/Shi-scid, IL-2Rγnull mouse model.
abstract: We expanded human T-lymphotropic virus type 1 Tax-specific CTL in vitro from PBMC of three individual adult T cell leukemia/lymphoma (ATL) patients and assessed their therapeutic potential in an in vivo model using NOG mice bearing primary ATL cells from the respective three patients (ATL/NOG). In these mice established with cells from a chronic-type patient, treatment by i.p. injection of autologous Tax-CTL resulted in greater infiltration of CD8-positive T cells into each ATL lesion. This was associated with a significant decrease of ATL cell infiltration into blood, spleen, and liver. Tax-CTL treatment also significantly decreased human soluble IL-2R concentrations in the sera. In another group of ATL/NOG mice, Tax-CTL treatment led to a significant prolongation of survival time. These findings show that Tax-CTL can infiltrate the tumor site, recognize, and kill autologous ATL cells in mice in vivo. In ATL/NOG mice with cells from an acute-type patient, whose postchemotherapeutic remission continued for >18 mo, antitumor efficacy of adoptive Tax-CTL therapy was also observed. However, in ATL/NOG mice from a different acute-type patient, whose ATL relapsed after 6 mo of remission, no efficacy was observed. Thus, although the therapeutic effects were different for different ATL patients, to the best of our knowledge, this is the first report that adoptive therapy with Ag-specific CTL expanded from a cancer patient confers antitumor effects, leading to significant survival benefit for autologous primary cancer cell-bearing mice in vivo. The present study contributes to research on adoptive CTL therapy, which should be applicable to several types of cancer.
authors.affiliation: Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Masaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Asahi
authors.initials: A
authors.lastname: Ito
authors.forename: Fumiko
authors.initials: F
authors.lastname: Mori
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.forename: Tomoko
authors.initials: T
authors.lastname: Narita
authors.forename: Tomiko
authors.initials: T
authors.lastname: Yamada
authors.forename: Masaki
authors.initials: M
authors.lastname: Ri
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kusumoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Komatsu
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D002908:Chronic Disease; D018920:Coculture Techniques; D004195:Disease Models, Animal; D016356:Gene Products, tax / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007274:Injections, Intraperitoneal; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency* / Q000235:genetics; D020014:K562 Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D061251:Primary Cell Culture; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation / Q000821:virology
chemical_list: D016356:Gene Products, tax; D053631:Interleukin Receptor Common gamma Subunit