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Blood Cancer J. 2016 Aug 12;6(8):e458. doi: 10.1038/bcj.2016.61.

Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts.

Author information

1
University Cancer Center (UCC), Carl Gustav Carus University Hospital TU-Dresden, Tumorimmunology, Dresden, Germany.
2
Cellex Patient Treatment GmbH, Dresden, Germany.
3
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
4
GEMoaB Monoclonals GmbH, Dresden, Germany.
5
University Hospital Carl Gustav Carus, Medical Clinic and Policlinic I, Dresden, Germany.

Abstract

The adoptive transfer of CD19-specific chimeric antigen receptor engineered T cells (CAR T cells) resulted in encouraging clinical trials in indolent B-cell malignancies. However, they also show the limitations of this fascinating technology: CAR T cells can lead to even life-threatening off-tumor, on-target side effects if CAR T cells crossreact with healthy tissues. Here, we describe a novel modular universal CAR platform technology termed UniCAR that reduces the risk of on-target side effects by a rapid and reversible control of CAR T-cell reactivity. The UniCAR system consists of two components: (1) a CAR for an inert manipulation of T cells and (2) specific targeting modules (TMs) for redirecting UniCAR T cells in an individualized time- and target-dependent manner. UniCAR T cells can be armed against different tumor targets simply by replacement of the respective TM for (1) targeting more than one antigen simultaneously or subsequently to enhance efficacy and (2) reducing the risk for development of antigen-loss tumor variants under treatment. Here we provide 'proof of concept' for retargeting of UniCAR T cells to CD33- and/or CD123-positive acute myeloid leukemia blasts in vitro and in vivo.

PMID:
27518241
PMCID:
PMC5022178
DOI:
10.1038/bcj.2016.61
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

MPB, AE and GE have filed patents and patent applications related to mAbs directed to CD33, La and the UniCAR platform technology. AE, SL and MC are employed by GEMoaB and CPT, respectively. The other authors declare no conflict of interest.

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