Format

Send to

Choose Destination
Oncotarget. 2017 Sep 18;8(65):108584-108603. doi: 10.18632/oncotarget.21017. eCollection 2017 Dec 12.

Development of novel target modules for retargeting of UniCAR T cells to GD2 positive tumor cells.

Author information

1
University Cancer Center (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany.
2
Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
3
German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
GEMoaB Monoclonals GmbH, Dresden, Germany.
5
Cellex Patient Treatment GmbH, Dresden, Germany.
6
Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany.
7
Medical Clinic and Policlinic I, University Hospital 'Carl Gustav Carus', TU Dresden, Dresden, Germany.
8
National Center for Tumor Diseases (NCT), Dresden, 'Carl Gustav Carus' TU Dresden, Dresden, Germany.
9
Department of Chemistry and Food Chemistry, School of Science, 'Carl Gustav Carus' TU Dresden, Germany.

Abstract

As the expression of a tumor associated antigen (TAA) is commonly not restricted to tumor cells, adoptively transferred T cells modified to express a conventional chimeric antigen receptor (CAR) might not only destroy the tumor cells but also attack target-positive healthy tissues. Furthermore, CAR T cells in patients with large tumor bulks will unpredictably proliferate and put the patients at high risk of adverse side effects including cytokine storms and tumor lysis syndrome. To overcome these problems, we previously established a modular CAR technology termed UniCAR: UniCAR T cells can repeatedly be turned on and off via dosing of a target module (TM). TMs are bispecific molecules which cross-link UniCAR T cells with target cells. After elimination of the respective TM, UniCAR T cells automatically turn off. Here we describe novel TMs against the disialoganglioside GD2 which is overexpressed in neuroectodermal but also many other tumors. In the presence of GD2-specific TMs, we see a highly efficient target-specific and -dependent activation of UniCAR T cells, secretion of pro-inflammatory cytokines, and tumor cell lysis both in vitro and experimental mice. According to PET-imaging, anti-GD2 TM enrich at the tumor site and are rapidly eliminated thus fulfilling all prerequisites of a UniCAR TM.

KEYWORDS:

CAR T cells; immunotherapy

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center