RT Journal Article
SR Electronic
T1 Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8<sup>+</sup> T Cells in Patients with Recurrent Glioblastoma
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 4062
OP 4072
DO 10.1158/1078-0432.CCR-15-0428
VO 21
IS 18
A1 Brown, Christine E.
A1 Badie, Behnam
A1 Barish, Michael E.
A1 Weng, Lihong
A1 Ostberg, Julie R.
A1 Chang, Wen-Chung
A1 Naranjo, Araceli
A1 Starr, Renate
A1 Wagner, Jamie
A1 Wright, Christine
A1 Zhai, Yubo
A1 Bading, James R.
A1 Ressler, Julie A.
A1 Portnow, Jana
A1 D'Apuzzo, Massimo
A1 Forman, Stephen J.
A1 Jensen, Michael C.
YR 2015
UL http://clincancerres.aacrjournals.org/content/21/18/4062.abstract
AB 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 108 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. Clin Cancer Res; 21(18); 4062–72. ©2015 AACR.