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Updated: Jan 9, 2026

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
Functional differences between CLL- and ALL-derived CAR T cells in a 3D tumor microenvironment highlight CXCR4 and
Janin Dingfelder1,2,3, Michael Aigner1,2,3, Jana Lindacher1,2,3
1Department of Internal Medicine 5, Hematology and Oncology Universitätsklinikum Erlangen Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) Erlangen Germany.
None:
Despite advances in targeted therapies, treatment of chronic lymphocytic leukemia (CLL) remains challenging, highlighting the urgent need for effective new therapeutic strategies. Although chimeric antigen receptor (CAR) T-cell therapy dramatically improved outcomes in acute lymphoblastic leukemia (ALL), its efficacy in CLL is limited. We hypothesize that this disparity results from pronounced CAR T-cell exhaustion and the immunosuppressive tumor microenvironment (TME) in CLL. We utilized an autologous 3D TME co-culture model to investigate the functionality of CAR T cells derived from CLL and ALL patients within physiologically relevant conditions. Our results revealed increased exhaustion levels and diminished cytotoxicity of CAR T cells from CLL patients compared to those from ALL patients. Importantly, combining CAR T-cell treatment with interleukin-10 (IL-10) or CXCR4 blockade effectively improved cytotoxicity against CLL cells, even in stromal-protected regions within the 3D model. These findings offer insights into CAR T-cell dysfunction in CLL and support novel TME-targeted combination strategies to improve clinical outcomes.
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