Preclinical evaluation of radiation and systemic, RGD-Targeted, adeno-Associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma

T. J. Quinn, N. Healy, A. Sara, E. Maggi, C. S. Claros, Rafi Kabarriti, L. Scandiuzzi, L. Liu, J. Gorecka, A. Adem, Indranil Basu, Z. Yuan, Chandan Guha

Research output: Contribution to journalArticle

Abstract

The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-Targeted adeno-Associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model. Furthermore, this combination appeared to modify the tumor microenvironment, resulting in decreased Tregs in the draining LN and increased tumor-Associated macrophages within the primary tumor. Finally, there appeared to be a reduction in metastatic potential and a prolongation of overall survival in the combined treatment group. These results indicate the use of targeted TNF gene therapy vector with radiation treatment could be a valuable treatment option for patients with metastatic melanoma.

Original languageEnglish (US)
Pages (from-to)13-19
Number of pages7
JournalCancer Gene Therapy
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2017

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Dependovirus
Genetic Therapy
Bacteriophages
Melanoma
Radiation
Therapeutics
Experimental Melanomas
Tumor Microenvironment
Neoplasms
Radiotherapy
Macrophages
Survival
Incidence

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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Preclinical evaluation of radiation and systemic, RGD-Targeted, adeno-Associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma. / Quinn, T. J.; Healy, N.; Sara, A.; Maggi, E.; Claros, C. S.; Kabarriti, Rafi; Scandiuzzi, L.; Liu, L.; Gorecka, J.; Adem, A.; Basu, Indranil; Yuan, Z.; Guha, Chandan.

In: Cancer Gene Therapy, Vol. 24, No. 1, 01.01.2017, p. 13-19.

Research output: Contribution to journalArticle

Quinn, T. J. ; Healy, N. ; Sara, A. ; Maggi, E. ; Claros, C. S. ; Kabarriti, Rafi ; Scandiuzzi, L. ; Liu, L. ; Gorecka, J. ; Adem, A. ; Basu, Indranil ; Yuan, Z. ; Guha, Chandan. / Preclinical evaluation of radiation and systemic, RGD-Targeted, adeno-Associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma. In: Cancer Gene Therapy. 2017 ; Vol. 24, No. 1. pp. 13-19.
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