Targeting tumor-associated endothelial cells: anti-VEGFR2 immunoliposomes mediate tumor vessel disruption and inhibit tumor growth.
Clin Cancer Res
; 18(2): 454-64, 2012 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-22065082
ABSTRACT
PURPOSE:
Angiogenesis is a key process in tumor progression. By binding VEGF, VEGF receptor-2 (VEGFR2) is a main signaling transducer in tumor-associated angiogenesis. Accordingly, therapeutic approaches against the VEGF/VEGFR2 signaling axis have been designed. However, an efficient and specific chemotherapeutic targeting of tumor-associated endothelial cells has not yet been achieved. EXPERIMENTALDESIGN:
We have employed anti-VEGFR2 antibodies covalently linked to pegylated liposomal doxorubicin (PLD) to specifically ablate tumor-associated endothelial cells in the Rip1Tag2 mouse model of insulinoma, in the MMTV-PyMT mouse model of breast cancer, and in the HT-29 human colon cancer xenograft transplantation model.RESULTS:
In each model, anti-VEGFR2-targeted immunoliposomes (ILs) loaded with doxorubicin (anti-VEGFR2-ILs-dox) were superior in therapeutic efficacy to empty liposomes, empty anti-VEGFR2-ILs, antibodies alone, and PLD. Efficacy was similar to that of the oral VEGFR1, -2, and -3 inhibitor PTK787. Detailed histopathologic and molecular analysis revealed a strong antiangiogenic effect of anti-VEGFR2-ILs-dox, and the observed antiangiogenic therapy was significantly more efficient in reducing tumor burden in well-vascularized transgenic mouse models as compared with the less-vascularized xenograft model.CONCLUSIONS:
Anti-VEGFR2 ILs provide a highly efficient approach to selectively deplete VEGFR2-expressing tumor vasculature. They offer a novel and promising anticancer strategy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
/
Imunotoxinas
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Inibidores da Angiogênese
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Receptor 2 de Fatores de Crescimento do Endotélio Vascular
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Células Endoteliais
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Insulinoma
/
Neoplasias Mamárias Experimentais
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Suíça