Sponsored by
Clin Cancer Res. 2012 Mar 8. [Epub ahead of print]
Brown CE, Starr R, Aguilar B, Shami A, Martinez C, D'Apuzzo M, Barish ME, Forman SJ, Jensen MC.
Source
Cancer Immunotherapy & Tumor Immunology and Hematology & Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope
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Abstract
PURPOSE:
To evaluate IL13Rα2 as an immunotherapeutic target for eliminating glioma stem-like initiating cells (GSC) of high-grade gliomas, with particular focus on the potential of genetically engineered IL13Rα2-specific primary human CD8+ cytotoxic T lymphocytes (IL13-zetakine+ CTL) to target this therapeutically resistant glioma subpopulation.
EXPERIMENTAL DESIGN:
A panel of low-passage GSC tumor sphere 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 while glioma IL13Rα2 expression varies between patients, for IL13Rα2pos 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 IL13Rα2pos GSC and IL13Rα2pos 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 anti-tumor activity against established IL13Rα2 pos GSC tumor sphere-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 utility of IL13Rα2-directed immunotherapeutic approaches for eradicating therapeutically resistant GSC populations.
PMID: 22407828 [PubMed - as supplied by publisher]