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Oncotarget. 2017 Dec 21;9(7):7487-7500. doi: 10.18632/oncotarget.23556. eCollection 2018 Jan 26.

Retargeting of UniCAR T cells with an in vivo synthesized target module directed against CD19 positive tumor cells.

Author information

1
University Cancer Center, Carl Gustav Carus TU Dresden, Tumor Immunology, Dresden, Germany.
2
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
3
GEMoaB Monoclonals GmbH, Dresden, Germany.
4
Leibniz Institute of Polymer Research Dresden, Dresden, Germany.
5
Cellex Patient Treatment GmbH, Dresden, Germany.
6
Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
7
German Cancer Consortium, Carl Gustav Carus TU Dresden, Dresden, Germany.
8
National Center for Tumor Diseases, Dresden, Carl Gustav Carus TU Dresden, Dresden, Germany.
9
Department of Chemistry and Food Chemistry, School of Science, TU Dresden, Dresden, Germany.

Abstract

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.

KEYWORDS:

CAR; CD19; T cell; T cell therapy; retargeting

Conflict of interest statement

CONFLICTS OF INTEREST AE and MPB have filed patents related to the UniCAR system. MPB, AE, and GE are shareholders of the company GEMoaB which ows the IP related to the UniCAR system. AE and GE are owners of the company Cellex PT which has licensed the CD19 UniCAR/TM combination. MC is an employer of Cellex PT.

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