Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

1 Publication
Switching CAR T cells on and off: A novel modular platform for retargeting of T cells to AML blasts
Cartellieri, M.; Feldmann, A.; Koristka, S.; Arndt, C.; Loff, S.; Ehninger, A.; von Bonin, M.; Bejestani, E. P.; Ehninger, G.; Bachmann, M. P.;
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 cross-react with healthy tissues.
Here, we describe a novel modular universal CAR platform technology termed UniCAR, which 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: (i) a CAR for an inert manipulation of T cells, and (ii) 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 (i) targeting more than one antigen simultaneously or subsequently to enhance efficacy, and (ii) 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 AML Blasts in vitro and in vivo.
Keywords: adoptive T cell therapy, acute myeloid leukemia, CD33, CD123, chimeric antigen receptor, targeted immunotherapy

Publ.-Id: 23750 - Permalink