Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity

E. Domingo-Musibay, C. Allen, C. Kurokawa, J. J. Hardcastle, I. Aderca, P. Msaouel, A. Bansal, H. Jiang, Timothy R DeGrado, Evanthia Galanis

Research output: Contribution to journalArticle

Abstract

Osteosarcoma (OS) is the most common primary bone tumor affecting children and young adults, and development of metastatic disease is associated with poor prognosis. The purpose of this study was to evaluate the antitumor efficacy of virotherapy with engineered measles virus (MV) vaccine strains in the treatment of OS. Cell lines derived from pediatric patients with OS (HOS, MG63, 143B, KHOS-312H, U2-OS and SJSA1) were infected with MV expressing green fluorescent protein (MV-GFP) and MV-expressing sodium iodide symporter (MV-NIS) strains. Viral gene expression and cytotoxicity as defined by syncytial formation, cell death and eradication of cell monolayers were demonstrated. Findings were correlated with in vivo efficacy in subcutaneous, orthotopic (tibial bone) and lung metastatic OS xenografts treated with the MV derivative MV-NIS via the intratumoral or intravenous route. Following treatment, we observed decrease in tumor growth of subcutaneous xenografts (P = 0.0374) and prolongation of survival in mice with orthotopic (Po0.0001) and pulmonary metastatic OS tumors (P = 0.0207). Expression of the NIS transgene in MV-NIS infected tumors allowed for single photon emission computed tomography and positron emission tomography-computed tomography imaging of virus infected tumors in vivo. Our data support the translational potential of MV-based virotherapy approaches in the treatment of recurrent and metastatic OS.

Original languageEnglish (US)
Pages (from-to)483-490
Number of pages8
JournalGene Therapy
Volume21
Issue number9
DOIs
StatePublished - Sep 11 2014

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Measles virus
Osteosarcoma
Interferons
Genes
Heterografts
Measles Vaccine
Bone and Bones
Neoplasms
Oncogenic Viruses
Lung
Viral Genes
Green Fluorescent Proteins
Single-Photon Emission-Computed Tomography
Transgenes
Young Adult
Cell Death
Therapeutics
Pediatrics
Gene Expression

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity. / Domingo-Musibay, E.; Allen, C.; Kurokawa, C.; Hardcastle, J. J.; Aderca, I.; Msaouel, P.; Bansal, A.; Jiang, H.; DeGrado, Timothy R; Galanis, Evanthia.

In: Gene Therapy, Vol. 21, No. 9, 11.09.2014, p. 483-490.

Research output: Contribution to journalArticle

Domingo-Musibay, E, Allen, C, Kurokawa, C, Hardcastle, JJ, Aderca, I, Msaouel, P, Bansal, A, Jiang, H, DeGrado, TR & Galanis, E 2014, 'Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity', Gene Therapy, vol. 21, no. 9, pp. 483-490. https://doi.org/10.1038/cgt.2014.54
Domingo-Musibay, E. ; Allen, C. ; Kurokawa, C. ; Hardcastle, J. J. ; Aderca, I. ; Msaouel, P. ; Bansal, A. ; Jiang, H. ; DeGrado, Timothy R ; Galanis, Evanthia. / Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity. In: Gene Therapy. 2014 ; Vol. 21, No. 9. pp. 483-490.
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