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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / metabolism*
  • Biocompatible Materials
  • Cell Line, Tumor
  • Cryogels / administration & dosage*
  • Humans
  • Immunotherapy / methods
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Neoplasms / therapy*
  • Tissue Scaffolds
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Bispecific
  • Biocompatible Materials
  • Cryogels