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

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

Author information

1
Department of Cancer Immunotherapy and Tumor Immunology, City of Hope Beckman Research Institute and Medical Center, Duarte, California. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Beckman Research Institute and Medical Center, Duarte, California. cbrown@coh.org.
2
Department of Neurosurgery, City of Hope Beckman Research Institute and Medical Center, Duarte, California.
3
Department of Neurosciences, City of Hope Beckman Research Institute and Medical Center, Duarte, California.
4
Department of Cancer Immunotherapy and Tumor Immunology, City of Hope Beckman Research Institute and Medical Center, Duarte, California. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Beckman Research Institute and Medical Center, Duarte, California.
5
Department of Cancer Immunotherapy and Tumor Immunology, City of Hope Beckman Research Institute and Medical Center, Duarte, California.
6
Department of Diagnostic Radiology, City of Hope Beckman Research Institute and Medical Center, Duarte, California.
7
Department of Medical Oncology and Therapeutics Research, City of Hope Beckman Research Institute and Medical Center, Duarte, California.
8
Department of Pathology, City of Hope Beckman Research Institute and Medical Center, Duarte, California.
9
Center for Childhood Cancer, Seattle Children's Research Institute, Seattle, Washington.

Abstract

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.

PMID:
26059190
PMCID:
PMC4632968
DOI:
10.1158/1078-0432.CCR-15-0428
[Indexed for MEDLINE]
Free PMC Article

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