Vector-producing tumor-tracking multipotent mesenchymal stromal cells for suicide cancer gene therapy

Abstract

Suicide cancer gene therapy with retroviral vector-producing cells was in the way of an adjuvant to the surgical resection of recurrent glioblastoma, although any benefit appeared to be marginal. It is likely that this therapeutic approach may have better outcomes if the vectors and transgenes are delivered more efficiently to the tumor cells. We have shown previously that tumor cells engineered by adenovirus-retrovirus hybrid vectors to produce retroviral progeny destroy satellite tumor cells. Whether the systemic delivery of vector-producing cells can effectively treat aggressive tumors remains to be determined. Effective retroviral vector delivery vehicles may be multipotent mesenchymal stromal cells (MSCs), which have been shown to home to tumor cells in vivo and deliver cancer-killing gene or immune products with minimal host rejection. Therefore, it may be possible to transduce tumors with recombinant progeny vectors delivered by MSCs. This may be particularly suitable for treating diffuse cancers like glioblastoma multiforme. While this strategy remains to be tested in various orthotopic or metastatic tumor models, it has the potential to greatly improve the outcome of suicide gene therapy.