2017, Aliperta, Roberta, Welzel, Petra B., Bergmann, Ralf, Freudenberg, Uwe, Berndt, Nicole, Feldmann, Anja, Arndt, Claudia, Koristka, Stefanie, Stanzione, Marcello, Cartellieri, Marc, Ehninger, Armin, Ehninger, Gerhard, Werner, Carsten, Pietzsch, Jens, Steinbach, Jörg, Bornhäuser, Martin, Bachmann, Michael P.

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.