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A multiprong approach to cancer gene therapy by coencapsulated cells

Cancer Gene Therapy volume 12, pages 369–380 (2005)Cite this article

Abstract

Immune-isolation of nonautologous cells with microencapsulation protects these cells from graft rejection, thus allowing the same recombinant therapeutic cell line to be implanted in different recipients. This approach was successful in treating HER2/neu-expressing tumors in mice by delivering an interleukin-2 fusion protein (sFvIL-2), or angiostatin. However, treatment with interleukin-2 led to profuse inflammation, while angiostatin delivery did not result in long-term tumor suppression, in part due to endothelial cell-independent neovascularization (vascular mimicry). We hypothesize that coencapsulating the two producer cells in the same microcapsules may enhance the efficacy and ameliorate the above side effects. Hence, B16-F0/neu tumor-bearing mice were implanted with sFvIL-2- and angiostatin-secreting cells coencapsulated in the same alginate-poly-L-lysine-alginate microcapsules. However, this protocol only produced an incremental but not synergistic improvement, as measured with greater tumor suppression and improved survival. Compared to the single sFvIL-2 treatment, the coencapsulation protocol showed improved efficacy associated with: mobilization of sFvIL-2 from the spleen; a higher level of cytokine delivery systemically and to the tumors; increased tumor and tumor-associated endothelial cell apoptosis; and a reduced host inflammatory response. However, compared to the single angiostatin treatment, the efficacy was reduced, primarily due to a “bystander” effect in which the angiostatin-secreting cells suffered similar transgene silencing as the coencapsulated cytokine-secreting cells. Nevertheless, the level of “vascular mimicry” of the single angiostatin treatment was significantly reduced. Hence, while there was no synergy in efficacy, an incremental improvement and some reduction in undesirable side effects of inflammation and vascular mimicry were achieved over the single treatments.

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Acknowledgements

We would like to thank the Canadian Breast Cancer Research Alliance and the Canadian Institute of Health Research for grant support and advice from Dr J Bourgeois in the pilot studies. Pasquale Cirone is the recipient of The David and Grace Prosser Scholarship, the McMaster University Graduate Scholarship and the Lee Nielson Roth Award for Medical Science (Cancer).

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Authors and Affiliations

  1. Department of Biology, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5

    Pasquale Cirone & Patricia L Chang

  2. Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5

    Feng Shen & Patricia L Chang

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  1. Pasquale Cirone
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  3. Patricia L Chang
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Correspondence to Patricia L Chang.

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Cirone, P., Shen, F. & Chang, P. A multiprong approach to cancer gene therapy by coencapsulated cells. Cancer Gene Ther 12, 369–380 (2005). https://doi.org/10.1038/sj.cgt.7700786

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