title: Preclinical evaluation of radiation and systemic, RGD-targeted, adeno-associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma.
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.
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Quinn
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: N
authors.initials: N
authors.lastname: Healy
authors.affiliation: Department of Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sara
authors.affiliation: Department of Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: Maggi
authors.affiliation: Department of Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Claros
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kabarriti
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Scandiuzzi
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gorecka
authors.affiliation: Department of Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Adem
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: I
authors.initials: I
authors.lastname: Basu
authors.affiliation: Department of Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Guha
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D008546:Melanoma, Experimental; D051379:Mice; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D009842:Oligopeptides / Q000378:metabolism*; D011878:Radiotherapy / Q000379:methods; D061089:Radiotherapy, Image-Guided; D016019:Survival Analysis; D016896:Treatment Outcome; D047368:Tumor Burden / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; C047981:arginyl-glycyl-aspartic acid