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Sci Rep. 2017 Feb 16;7:42855. doi: 10.1038/srep42855.

Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy.

Author information

1
Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.
2
Leibniz Institute of Polymer Research Dresden (IPF), Hohe Strasse 6, 01069 Dresden, Germany.
3
Institute of Physiological Chemistry, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
4
Cellex Patient Treatment GmbH, Tatzberg 47, 01307 Dresden, Germany.
5
University Cancer Center (UCC), Technische Universität Dresden, Tumorimmunology, Fetscherstrasse 74, 01307 Dresden, Germany.
6
GEMoaB Monoclonals GmbH, Tatzberg 47, 01307 Dresden, Germany.
7
Medical Clinic and Policlinic I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
8
DKTK (German consortium for Translational Cancer Research), Dresden, Germany.
9
National Center for Tumor Diseases (NCT), Dresden, 'Carl Gustav Carus' TU Dresden, Dresden, Germany.
10
DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
11
Department of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, 01069 Dresden, Germany.

Abstract

Combining stem cells with biomaterial scaffolds provides a promising strategy for the development of drug delivery systems. Here we propose an innovative immunotherapeutic organoid by housing human mesenchymal stromal cells (MSCs), gene-modified for the secretion of an anti-CD33-anti-CD3 bispecific antibody (bsAb), in a small biocompatible star-shaped poly(ethylene glycol)-heparin cryogel scaffold as a transplantable and low invasive therapeutic machinery for the treatment of acute myeloid leukemia (AML). The macroporous biohybrid cryogel platform displays effectiveness in supporting proliferation and survival of bsAb-releasing-MSCs overtime in vitro and in vivo, avoiding cell loss and ensuring a constant release of sustained and detectable levels of bsAb capable of triggering T-cell-mediated anti-tumor responses and a rapid regression of CD33+ AML blasts. This therapeutic device results as a promising and safe alternative to the continuous administration of short-lived immunoagents and paves the way for effective bsAb-based therapeutic strategies for future tumor treatments.

PMID:
28205621
PMCID:
PMC5311951
DOI:
10.1038/srep42855
[Indexed for MEDLINE]
Free PMC Article

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