Preclinical evaluation of radiation and systemic, RGD-targeted, adeno-associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma.
Cancer Gene Ther
; 24(1): 13-19, 2017 Jan.
Article
em En
| MEDLINE
| ID: mdl-27934883
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.
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Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Fator de Necrose Tumoral alfa
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Dependovirus
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Vetores Genéticos
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Melanoma
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article