Targeted Cancer Therapy Using Fusion Protein of TNFα and Tumor-Associated Fibronectin-Specific Aptide.
Mol Pharm
; 14(11): 3772-3779, 2017 11 06.
Article
en En
| MEDLINE
| ID: mdl-28969419
ABSTRACT
Tumor necrosis factor-α has shown potent antitumor effects in preclinical and clinical studies. However, severe side effects at less than therapeutic doses have limited its systemic delivery, prompting the need for a new strategy for targeted delivery of the protein to tumors. Here, we report a fusion protein of mouse tumor necrosis factor (TNF)-α (mTNFα) and a cancer-targeting, high-affinity aptide and investigate its therapeutic efficacy in tumor-bearing mice. A fusion protein consisting of mTNFα, a linker, and an aptide specific to extra domain B (EDB) of fibronectin (APTEDB), designated mTNFα-APTEDB, was successfully produced by expression in Escherichia coli. mTNFα-APTEDB retained specificity and affinity for its target, EDB. In mice bearing EDB-overexpressing fibrosarcomas, mTNFα-APTEDB showed greater efficacy in inhibiting tumor growth than mTNFα alone or mTNFα linked to a nonrelevant aptide, without causing an appreciable loss in body weight. Moreover, in vivo antitumor efficacy was further significantly increased by combination treatment with the chemotherapeutic drug, melphalan, suggesting a synergistic effect attributable to enhanced drug uptake into the tumor as a result of TNFα-mediated enhanced vascular permeability. These results suggest that a fusion protein of mTNFα with a cancer-targeting peptide could be a new anticancer therapeutic option for ensuring potent antitumor efficacy after systemic delivery.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Péptidos
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Proteínas Recombinantes de Fusión
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Fibronectinas
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Factor de Necrosis Tumoral alfa
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Pharm
Asunto de la revista:
BIOLOGIA MOLECULAR
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FARMACIA
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FARMACOLOGIA
Año:
2017
Tipo del documento:
Article