Autologous Tax-specific CTL therapy in a primary adult T cell leukemia/lymphoma cell-bearing NOD/Shi-scid, IL-2Rγnull mouse model

J Immunol. 2013 Jul 1;191(1):135-44. doi: 10.4049/jimmunol.1202692. Epub 2013 Jun 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Chronic Disease
  • Coculture Techniques
  • Disease Models, Animal
  • Gene Products, tax / administration & dosage
  • Gene Products, tax / immunology*
  • Gene Products, tax / therapeutic use*
  • Human T-lymphotropic virus 1 / immunology*
  • Humans
  • Immunotherapy, Adoptive / methods
  • Injections, Intraperitoneal
  • Interleukin Receptor Common gamma Subunit / deficiency*
  • Interleukin Receptor Common gamma Subunit / genetics
  • K562 Cells
  • Leukemia-Lymphoma, Adult T-Cell / immunology*
  • Leukemia-Lymphoma, Adult T-Cell / therapy*
  • Leukemia-Lymphoma, Adult T-Cell / virology
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Primary Cell Culture
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / transplantation
  • T-Lymphocytes, Cytotoxic / virology

Substances

  • Gene Products, tax
  • Interleukin Receptor Common gamma Subunit