当前位置： SCI文献检索 > CANCER RESEARCH期刊下所有文献 > Coupling tumor necrosis factor-alpha with alphaV integrin ligands improves its antineoplastic activity.

Coupling tumor necrosis factor-alpha with alphaV integrin ligands improves its antineoplastic activity.

Abstract：

:Despite the impressive results obtained in animal models, the clinical use of tumor necrosis factor-alpha (TNF) as an anticancer drug is limited by severe toxicity. We have shown previously that targeted delivery of TNF to aminopeptidase N (CD13), a marker of angiogenic vessels, improved the therapeutic index of this cytokine in tumor-bearing mice. To assess whether the vascular-targeting approach could be extended to other markers of tumor blood vessels, in this work, we have fused TNF with the ACDCRGDCFCG peptide, a ligand of alpha(V) integrins by recombinant DNA technology. We have found that subnanogram doses of this conjugate are sufficient to induce antitumor effects in tumor-bearing mice when combined with melphalan, a chemotherapeutic drug. Cell adhesion assays and competitive binding experiments with anti-integrin antibodies showed that the Arg-Gly-Asp moiety interacts with cell adhesion receptors, including alpha(V)beta(3) integrin, as originally postulated. In addition, ACGDRGDCFCG-mouse TNF conjugate induced cytotoxic effects in standard cytolytic assays, implying that ACGDRGDCFCG-mouse TNF conjugate can also bind TNF receptors and trigger death signals. These results indicate that coupling TNF with alpha(V) integrin ligands improves its antineoplastic activity and supports the concept that vascular targeting is a strategy potentially applicable to different endothelial markers, not limited to CD13.

journal_name

Cancer Res

journal_title

Cancer research

authors

Curnis F,Gasparri A,Sacchi A,Longhi R,Corti A

doi

10.1158/0008-5472.can-03-1753

subject

Has Abstract

pub_date

2004-01-15 00:00:00

pages

565-71

issue

2

eissn

0008-5472

issn

1538-7445

journal_volume

64

pub_type

杂志文章

相关文献

CANCER RESEARCH文献大全