Retargeting of UniCAR T cells with an in vivo synthesized target module directed against CD19 positive tumor cells
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Dominik Bachmann1, Roberta Aliperta1,*, Ralf Bergmann2,*, Anja Feldmann2,*, Stefanie Koristka2,*, Claudia Arndt2,*, Simon Loff3,*, Petra Welzel4, Susann Albert1, Alexandra Kegler2, Armin Ehninger3, Marc Cartellieri5, Gerhard Ehninger6,7,8, Martin Bornhäuser6,7,8, Malte von Bonin6, Carsten Werner4, Jens Pietzsch2,9, Jörg Steinbach2,7,8,9 and Michael Bachmann1,2,7,8
1University Cancer Center, Carl Gustav Carus TU Dresden, Tumor Immunology, Dresden, Germany
2Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany
3GEMoaB Monoclonals GmbH, Dresden, Germany
4Leibniz Institute of Polymer Research Dresden, Dresden, Germany
5Cellex Patient Treatment GmbH, Dresden, Germany
6Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
7German Cancer Consortium, Carl Gustav Carus TU Dresden, Dresden, Germany
8National Center for Tumor Diseases, Dresden, Carl Gustav Carus TU Dresden, Dresden, Germany
9Department of Chemistry and Food Chemistry, School of Science, TU Dresden, Dresden, Germany
*These authors contributed equally to this work
Michael Bachmann, email: [email protected]
Keywords: CAR; CD19; retargeting; T cell; T cell therapy
Received: October 09, 2017 Accepted: October 27, 2017 Published: December 21, 2017
Recent treatments of leukemias with T cells expressing chimeric antigen receptors (CARs) underline their impressive therapeutic potential but also their risk of severe side effects including cytokine release storms and tumor lysis syndrome. In case of cross-reactivities, CAR T cells may also attack healthy tissues. To overcome these limitations, we previously established a switchable CAR platform technology termed UniCAR. UniCARs are not directed against typical tumor-associated antigens (TAAs) but instead against a unique peptide epitope: Fusion of this peptide epitope to a recombinant antibody domain results in a target module (TM). TMs can cross-link UniCAR T cells with tumor cells and thereby lead to their destruction. So far, we constructed TMs with a short half-life. The fast turnover of such a TM allows to rapidly interrupt the treatment in case severe side effects occur. After elimination of most of the tumor cells, however, longer lasting TMs which have not to be applied via continous infusion would be more convenient for the patient. Here we describe and characterize a TM for retargeting UniCAR T cells to CD19 positive tumor cells. Moreover, we show that the TM can efficiently be produced in vivo from producer cells housed in a sponge-like biomimetic cryogel and, thereby, serving as an in vivo TM factory for an extended retargeting of UniCAR T cells to CD19 positive leukemic cells.
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