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

Cancer Gene Therapy volume 18, pages 553–562 (2011)Cite this article

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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.

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Acknowledgements

This work was supported in part by the Swiss National Science Foundation (PNR 37), the Swiss Confederation's innovation promotion agency in collaboration with MaxiVAX SA, la Ligue genevoise contre le cancer and la Fondation pour la lutte contre le cancer.

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Authors and Affiliations

  1. Department of Oncology, Geneva University Hospital and Medical School, Geneva, Switzerland

    F Schwenter, S Zarei, P Luy & N Mach

  2. Department of Visceral and Transplantation Surgery, Geneva University Hospital and Medical School, Geneva, Switzerland

    F Schwenter & P Morel

  3. Life Sciences Department, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

    V Padrun & N Bouche

  4. Department of Genetics, Harvard Medical School and Harvard Gene Therapy Initiative, Boston, MA, USA

    J S Lee & R C Mulligan

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  1. F Schwenter
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Correspondence to F Schwenter.

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N Mach is stocks owners of MaxiVAX SA. The other authors declare no conflict of interest.

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Schwenter, F., Zarei, S., Luy, P. et al. Cell encapsulation technology as a novel strategy for human anti-tumor immunotherapy. Cancer Gene Ther 18, 553–562 (2011). https://doi.org/10.1038/cgt.2011.22

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