Cell encapsulation technology as a novel strategy for human anti-tumor immunotherapy

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant in autologous cell-based anti-tumor immunotherapy has recently been approved for clinical application. To avoid the need for individualized processing of autologous cells, we developed a novel strategy based on the encapsulation of GM-CSF-secreting human allogeneic cells. GM-CSF-producing K562 cells showed high, stable and reproducible cytokine secretion when enclosed into macrocapsules. For clinical development, the cryopreservation of these devices is critical. Thawing of capsules frozen at different time points displayed differences in GM-CSF release shortly after thawing. However, similar secretion values to those of non-frozen control capsules were obtained 8 days after thawing at a rate of >1000 ng GM-CSF per capsule every 24 h. For future human application, longer and reinforced capsules were designed. After irradiation and cryopreservation, these capsules produced >300 ng GM-CSF per capsule every 24 h 1 week after thawing. The in vivo implantation of encapsulated K562 cells was evaluated in mice and showed preserved cell survival. Finally, as a proof of principle of biological activity, capsules containing B16-GM-CSF allogeneic cells implanted in mice induced a prompt inflammatory reaction. The ability to reliably achieve high adjuvant release using a standardized procedure may lead to a new clinical application of GM-CSF in cell-based cancer immunization

A high-capacity cell macroencapsulation system supporting the long-term survival of genetically engineered allogeneic cells

“…This illustrates the remarkable capacity of engineered C2C12 mouse myoblasts to adapt to restrictive conditions in encapsulation devices, while maintaining a high level of recombinant protein production in vivo (see Ref. [40]) [27,28].…”

Toward Customized Extracellular Niche Engineering: Progress in Cell‐Entrapment Technologies

“…Several other polymeric encapsulation devices made of poly(urethane), poly(ether sulfone), polypropylene have been tested with cell types such as pancreatic islets, myoblasts, hepatocytes, B16 melanoma cells and fibroblasts . The major disadvantage of these materials is the absence of cellular recognition sites and high hydrophobic nature that is associated with protein adsorption, making it susceptible to inflammatory reactions.…”

Droplet‐Based Microfluidic Templating of Polyglycerol‐Based Microgels for the Encapsulation of Cells: A Comparative Study

“…These features make our new synthetic matrix an excellent candidate for the encapsulation and potential transplantation of cells for the delivery of therapeutics. A long‐term immunoisolation of the cells would allow production and on‐demand release of the hormones, factors, or enzymes, the absence of which causes various diseases …”

“…Biologically relevant, immune‐privileged cells hold promise for the treatment of diseases that require a prolonged minute‐to‐minute regulation of a metabolite . Hence today cell encapsulation has attracted much attention and constitutes a largely researched field with a broad spectrum of applications such as in neurodegenerative diseases, myocardial regeneration, chronic anemia, bone and cartilage defects, cancer, and diabetes mellitus …”