Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma

Clin Cancer Res. 2015 Sep 15;21(18):4062-72. doi: 10.1158/1078-0432.CCR-15-0428. Epub 2015 Jun 9.


Purpose: A first-in-human pilot safety and feasibility trial evaluating chimeric antigen receptor (CAR)-engineered, autologous primary human CD8(+) cytotoxic T lymphocytes (CTL) targeting IL13Rα2 for the treatment of recurrent glioblastoma (GBM).

Experimental design: Three patients with recurrent GBM were treated with IL13(E13Y)-zetakine CD8(+) CTL targeting IL13Rα2. Patients received up to 12 local infusions at a maximum dose of 10(8) CAR-engineered T cells via a catheter/reservoir system.

Results: We demonstrate the feasibility of manufacturing sufficient numbers of autologous CTL clones expressing an IL13(E13Y)-zetakine CAR for redirected HLA-independent IL13Rα2-specific effector function for a cohort of patients diagnosed with GBM. Intracranial delivery of the IL13-zetakine(+) CTL clones into the resection cavity of 3 patients with recurrent disease was well-tolerated, with manageable temporary brain inflammation. Following infusion of IL13-zetakine(+) CTLs, evidence for transient anti-glioma responses was observed in 2 of the patients. Analysis of tumor tissue from 1 patient before and after T-cell therapy suggested reduced overall IL13Rα2 expression within the tumor following treatment. MRI analysis of another patient indicated an increase in tumor necrotic volume at the site of IL13-zetakine(+) T-cell administration.

Conclusions: These findings provide promising first-in-human clinical experience for intracranial administration of IL13Rα2-specific CAR T cells for the treatment of GBM, establishing a foundation on which future refinements of adoptive CAR T-cell therapies can be applied.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain / pathology
  • Brain Neoplasms / immunology
  • Brain Neoplasms / therapy*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Feasibility Studies
  • Female
  • Glioblastoma / immunology
  • Glioblastoma / therapy*
  • Glioma / immunology
  • Glioma / therapy
  • HLA Antigens / chemistry
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Inflammation
  • Interleukin-13 Receptor alpha2 Subunit / therapeutic use*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Patient Safety
  • Pilot Projects
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / therapeutic use*
  • Recurrence
  • Treatment Outcome
  • Young Adult


  • HLA Antigens
  • IL13-zetakine
  • Interleukin-13 Receptor alpha2 Subunit
  • Receptors, Antigen, T-Cell