title: Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells.
abstract: OBJECTIVE
  To evaluate IL13Rα2 as an immunotherapeutic target for eliminating glioma stem-like cancer initiating cells (GSC) of high-grade gliomas, with particular focus on the potential of genetically engineered IL13Rα2-specific primary human CD8(+) CTLs (IL13-zetakine(+) CTL) to target this therapeutically resistant glioma subpopulation.
  
  
  METHODS
  A panel of low-passage GSC tumor sphere (TS) and serum-differentiated glioma lines were expanded from patient glioblastoma specimens. These glioblastoma lines were evaluated for expression of IL13Rα2 and for susceptibility to IL13-zetakine(+) CTL-mediated killing in vitro and in vivo.
  
  
  RESULTS
  We observed that although glioma IL13Rα2 expression varies between patients, for IL13Rα2(pos) cases this antigen was detected on both GSCs and more differentiated tumor cell populations. IL13-zetakine(+) CTL were capable of efficient recognition and killing of both IL13Rα2(pos) GSCs and IL13Rα2(pos) differentiated cells in vitro, as well as eliminating glioma-initiating activity in an orthotopic mouse tumor model. Furthermore, intracranial administration of IL13-zetakine(+) CTL displayed robust antitumor activity against established IL13Rα2(pos) GSC TS-initiated orthotopic tumors in mice.
  
  
  CONCLUSIONS
  Within IL13Rα2 expressing high-grade gliomas, this receptor is expressed by GSCs and differentiated tumor populations, rendering both targetable by IL13-zetakine(+) CTLs. Thus, our results support the potential usefullness of IL13Rα2-directed immunotherapeutic approaches for eradicating therapeutically resistant GSC populations.
authors.affiliation: Department of Cancer Immunotherapy & Tumor Immunology and Hematology & Hematopoietic Cell Transplantation, Pathology, and Neurosciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA. cbrown@coh.org
authors.forename: Christine E
authors.initials: CE
authors.lastname: Brown
authors.forename: Renate
authors.initials: R
authors.lastname: Starr
authors.forename: Brenda
authors.initials: B
authors.lastname: Aguilar
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Shami
authors.forename: Catalina
authors.initials: C
authors.lastname: Martinez
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Apuzzo
authors.forename: Michael E
authors.initials: ME
authors.lastname: Barish
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jensen
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D018793:Interleukin-13 / Q000276:immunology*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D011994:Recombinant Proteins