Research Papers:

Patient-derived glioblastoma stem cells are killed by CD133-specific CAR T cells but induce the T cell aging marker CD57

Xuekai Zhu _, Shruthi Prasad, Simone Gaedicke, Michael Hettich, Elke Firat and Gabriele Niedermann

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Oncotarget. 2015; 6:171-184. https://doi.org/10.18632/oncotarget.2767

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Xuekai Zhu1, Shruthi Prasad1,2, Simone Gaedicke1, Michael Hettich1,2, Elke Firat1 and Gabriele Niedermann1,3

1 Department of Radiation Oncology, University Hospital Freiburg, Freiburg, Germany

2 Faculty of Biology, University of Freiburg, Freiburg, Germany

3 German Cancer Consortium (DKTK), Freiburg, and German Cancer Research Center (DKFZ), Heidelberg, Germany


Gabriele Niedermann, email:

Keywords: chimeric antigen receptor, cancer stem cell, glioblastoma, immunotherapy, CD57

Received: October 10, 2014 Accepted: November 14, 2014 Published: November 15, 2014


The AC133 epitope of CD133 is a cancer stem cell (CSC) marker for many tumor entities, including the highly malignant glioblastoma multiforme (GBM). We have developed an AC133-specific chimeric antigen receptor (CAR) and show that AC133-CAR T cells kill AC133+ GBM stem cells (GBM-SCs) both in vitro and in an orthotopic tumor model in vivo. Direct contact with patient-derived GBM-SCs caused rapid upregulation of CD57 on the CAR T cells, a molecule known to mark terminally or near-terminally differentiated T cells. However, other changes associated with terminal T cell differentiation could not be readily detected. CD57 is also expressed on tumor cells of neural crest origin and has been preferentially found on highly aggressive, undifferentiated, multipotent CSC-like cells. We found that CD57 was upregulated on activated T cells only upon contact with CD57+ patient-derived GBM-SCs, but not with conventional CD57-negative glioma lines. However, CD57 was not downregulated on the GBM-SCs upon their differentiation, indicating that this molecule is not a bona fide CSC marker for GBM. Differentiated GBM cells still induced CD57 on CAR T cells and other activated T cells. Therefore, CD57 can apparently be upregulated on activated human T cells by mere contact with CD57+ target cells.

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