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Cryogel-Supported Stem Cell Factory for Customized Sustained Release of Bispecific Antibodies for Cancer Immunotherapy

Aliperta, R.; Welzel, P. B.; Bergmann, R.; Freudenberg, R.; 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.

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.

Keywords: starPEG-heparin cryogel; Mesenchymal stromal cells; Bispecific antibody; Cancer immunotherapy

Permalink: https://www.hzdr.de/publications/Publ-23663
Publ.-Id: 23663