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Open Access 01-09-2019 | Original Article

Anti-CAR-engineered T cells for epitope-based elimination of autologous CAR T cells

Authors: Stefanie Koristka, Pauline Ziller-Walter, Ralf Bergmann, Claudia Arndt, Anja Feldmann, Alexandra Kegler, Marc Cartellieri, Armin Ehninger, Gerhard Ehninger, Martin Bornhäuser, Michael P. Bachmann

Published in: Cancer Immunology, Immunotherapy | Issue 9/2019

Abstract

Although CAR T-cell therapy has demonstrated tremendous clinical efficacy especially in hematological malignancies, severe treatment-associated toxicities still compromise the widespread application of this innovative technology. Therefore, developing novel approaches to abrogate CAR T-cell-mediated side effects is of great relevance. Several promising strategies pursue the selective antibody-based depletion of adoptively transferred T cells via elimination markers. However, given the limited half-life and tissue penetration, dependence on the patients’ immune system and on-target/off-side effects of proposed monoclonal antibodies, we sought to exploit αCAR-engineered T cells to efficiently eliminate CAR T cells. For comprehensive and specific recognition, a small peptide epitope (E-tag) was incorporated into the extracellular spacer region of CAR constructs. We provide first proof-of-concept for targeting this epitope by αE-tag CAR T cells, allowing an effective killing of autologous E-tagged CAR T cells both in vitro and in vivo whilst sparing cells lacking the E-tag. In addition to CAR T-cell cytotoxicity, the αE-tag-specific T cells can be empowered with cancer-fighting ability in case of relapse, hence, have versatile utility. Our proposed methodology can most probably be implemented in CAR T-cell therapies regardless of the targeted tumor antigen aiding in improving overall safety and survival control of highly potent gene-modified cells.

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Title: Anti-CAR-engineered T cells for epitope-based elimination of autologous CAR T cells
Authors: Stefanie Koristka
Pauline Ziller-Walter
Ralf Bergmann
Claudia Arndt
Anja Feldmann
Alexandra Kegler
Marc Cartellieri
Armin Ehninger
Gerhard Ehninger
Martin Bornhäuser
Michael P. Bachmann
Publication date: 01-09-2019
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 9/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02376-y

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