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Authors
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Aliperta, R. ; Welzel, P. ; Bergmann, R. ; Freudenberg, U. ; Berndt, N. ; Feldmann, A. ; Arndt, C. ; Koristka, S. ; Stanzione, M. ; Cartellieri, M. ; Ehninger, A. ; Ehninger, G. ; Werner, C. ; Pietzsch, J. ; Steinbach, J. ; Bornhäuser, M. ; Bachmann, M.
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Title
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Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy
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Date
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16.02.2017
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Number
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50062
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Abstract
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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.
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Publisher
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Scientific Reports
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Wikidata
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Citation
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Scientific Reports 7 (2017) Art.No. 42855
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DOI
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https://doi.org/10.1038/srep42855
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Tags
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