title: Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy.
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.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Roberta
authors.initials: R
authors.lastname: Aliperta
authors.affiliation: Leibniz Institute of Polymer Research Dresden (IPF), Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Petra B
authors.initials: PB
authors.lastname: Welzel
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bergmann
authors.affiliation: Leibniz Institute of Polymer Research Dresden (IPF), Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Freudenberg
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Berndt
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Feldmann
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Arndt
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Koristka
authors.affiliation: Institute of Physiological Chemistry, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Marcello
authors.initials: M
authors.lastname: Stanzione
authors.affiliation: Cellex Patient Treatment GmbH, Tatzberg 47, 01307 Dresden, Germany.|University Cancer Center (UCC), Technische Universität Dresden, Tumorimmunology, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Cartellieri
authors.affiliation: GEMoaB Monoclonals GmbH, Tatzberg 47, 01307 Dresden, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Ehninger
authors.affiliation: Medical Clinic and Policlinic I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.|DKTK (German consortium for Translational Cancer Research), Dresden, Germany.|National Center for Tumor Diseases (NCT), Dresden, 'Carl Gustav Carus' TU Dresden, Dresden, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Leibniz Institute of Polymer Research Dresden (IPF), Hohe Strasse 6, 01069 Dresden, Germany.|DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.|Department of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, 01069 Dresden, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.|Department of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, 01069 Dresden, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.affiliation: Medical Clinic and Policlinic I, University Hospital 'Carl Gustav Carus', Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.|DKTK (German consortium for Translational Cancer Research), Dresden, Germany.|National Center for Tumor Diseases (NCT), Dresden, 'Carl Gustav Carus' TU Dresden, Dresden, Germany.|DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, 01328 Dresden, Germany.|DKTK (German consortium for Translational Cancer Research), Dresden, Germany.|National Center for Tumor Diseases (NCT), Dresden, 'Carl Gustav Carus' TU Dresden, Dresden, Germany.|DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000378:metabolism*; D001672:Biocompatible Materials; D045744:Cell Line, Tumor; D059985:Cryogels / Q000008:administration & dosage*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D054457:Tissue Scaffolds; D023041:Xenograft Model Antitumor Assays
chemical_list: D018033:Antibodies, Bispecific; D001672:Biocompatible Materials; D059985:Cryogels