Optimising measles virus-guided radiovirotherapy with external beam radiotherapy and specific checkpoint kinase 1 inhibition.
Radiother Oncol
; 108(1): 24-31, 2013 Jul.
Article
en En
| MEDLINE
| ID: mdl-23849174
BACKGROUND AND PURPOSE: We previously reported a therapeutic strategy comprising replication-defective NIS-expressing adenovirus combined with radioiodide, external beam radiotherapy (EBRT) and DNA repair inhibition. We have now evaluated NIS-expressing oncolytic measles virus (MV-NIS) combined with NIS-guided radioiodide, EBRT and specific checkpoint kinase 1 (Chk1) inhibition in head and neck and colorectal models. MATERIALS AND METHODS: Anti-proliferative/cytotoxic effects of individual agents and their combinations were measured by MTS, clonogenic and Western analysis. Viral gene expression was measured by radioisotope uptake and replication by one-step growth curves. Potential synergistic interactions were tested in vitro by Bliss independence analysis and in in vivo therapeutic studies. RESULTS: EBRT and MV-NIS were synergistic in vitro. Furthermore, EBRT increased NIS expression in infected cells. SAR-020106 was synergistic with EBRT, but also with MV-NIS in HN5 cells. MV-NIS mediated (131)I-induced cytotoxicity in HN5 and HCT116 cells and, in the latter, this was enhanced by SAR-020106. In vivo studies confirmed that MV-NIS, EBRT and Chk1 inhibition were effective in HCT116 xenografts. The quadruplet regimen of MV-NIS, virally-directed (131)I, EBRT and SAR-020106 had significant anti-tumour activity in HCT116 xenografts. CONCLUSION: This study strongly supports translational and clinical research on MV-NIS combined with radiation therapy and radiosensitising agents.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
/
Pirazinas
/
Fármacos Sensibilizantes a Radiaciones
/
Neoplasias Colorrectales
/
Inhibidores de Proteínas Quinasas
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Viroterapia Oncolítica
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Neoplasias de Cabeza y Cuello
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Radioisótopos de Yodo
/
Isoquinolinas
/
Virus del Sarampión
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Radiother Oncol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido
Pais de publicación:
Irlanda