Entrapment of retroviral vector producer cells in three-dimensional alginate scaffolds for potential use in cancer gene therapy

Mona Dvir-Ginzberg, Alexander Konson, Smadar Cohen, Riad Agbaria

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

We explored the possibility of entrapping retroviral vector producing cells (VPC) within porous 3D matrix to induce a local and sustained release of viral particles to the malignant milieu. PA317/STK, which constantly shed reroviral vectors, was used to transduce cancer cells with the herpes simplex virus thymidine kinase (HSV-tk) gene. Once HSV-tk is expressed, it preferentially phosphorylates nucleoside analog prodrugs, such as ganciclovir (GCV) and N-methanocarbathymidine (N-MCT), to their active triphosphate metabolites, which when incorporated into cellular DNA cause cell death. PA317/STK cells were seeded within 3D alginate scaffold at two different cell densities via static seeding procedure. In vitro assays determined that PA317/STK seeded at high-cell density in scaffolds maintained constant cell number, low cell leakage, and spheroid morphology with viral vector transfection activity. Postcell-seeding viral vector activity was confirmed by transfection of murine colon cancer cells (MC38) with conditioned media originated from VPC-containing scaffolds and the subsequent ability to generate N-MCT triphosphate. Preliminary in vivo transplantation of VPC-containing scaffolds into the peritoneal cavity of mice bearing intraperitoneal MC38 tumors with 2 weeks subsequent GCV administration resulted in a significantly higher survival rate relative to control groups. Our results demonstrate the feasibility of employing alginate scaffolds to efficiently entrap and support PA317/STK cells for cancer gene therapy.

Original languageEnglish
Pages (from-to)59-66
Number of pages8
JournalJournal of Biomedical Materials Research - Part B Applied Biomaterials
Volume80
Issue number1
DOIs
StatePublished - 1 Jan 2007

Keywords

  • Alginate scaffold
  • Cancer
  • Ganciclovir
  • Local release
  • Suicide gene therapy

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