Comparative pharmacokinetics of a tumour-targeting therapy candidate rh-IFNα2a–NGR with rh-IFNα2a administered intravenously in mice and rats

Wang, Xuexi; Li, Lu; Song, Chunli; Qian, Weina; Zhang, Sheng-Yan; Zhang, Yingqi; Wu, Yongjie

doi:10.1111/jphp.12022

Cited by 1 publication

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References 19 publications

(19 reference statements)

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“…Other investigators showed that the anti-tumor activity of IFNα2a can also be increased by coupling this protein with an NGR peptide [ 85 ]. Studies performed in animal models showed that the IFNα2a-NGR conjugate, but not IFNα2a, accumulates and target tumor vessels [ 86 – 88 ].…”

Section: The Ngr-mediated Targeting Of Cytokines To Tumor Vasculaturementioning

confidence: 99%

Peptide-Mediated Targeting of Cytokines to Tumor Vasculature: The NGR-hTNF Example

et al. 2013

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A growing body of evidence suggests that the efficacy of cytokines in cancer therapy can be increased by targeting strategies based on conjugation with ligands that recognize receptors expressed by tumor cells or elements of the tumor microenvironment, including the tumor vasculature. The targeting approach is generally conceived to permit administration of low, yet pharmacologically active, doses of drugs, thereby avoiding toxic reactions. However, it is becoming clear that, in the case of cytokines, this strategy has another inherent advantage, i.e. the possibility of administering extremely low doses that do not activate systemic counter-regulatory mechanisms, which may limit their potential therapeutic effects. This review is focused on the use of tumor vasculature-homing peptides as vehicles for targeted delivery of cytokines to tumor blood vessel. In particular, we provide an overview of peptide-cytokine conjugates made with peptides containing the NGR, RGD, isoDGR or RGR sequences and describe, in more details, the biological and pharmacological properties of NGR-hTNF, a peptide-tumor necrosis factor-α conjugate that is currently being tested in phase II and III clinical studies. The results of preclinical and clinical studies performed with these products suggest that peptide-mediated vascular-targeting is indeed a viable strategy for delivering bioactive amounts of cytokines to tumor endothelial cells without causing the activation of counter-regulatory mechanisms and toxic reactions.

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Section: The Ngr-mediated Targeting Of Cytokines To Tumor Vasculaturementioning

confidence: 99%

Peptide-Mediated Targeting of Cytokines to Tumor Vasculature: The NGR-hTNF Example

et al. 2013

View full text Add to dashboard Cite

show abstract

Comparative pharmacokinetics of a tumour-targeting therapy candidate rh-IFNα2a–NGR with rh-IFNα2a administered intravenously in mice and rats

Abstract: rh-IFNα2a-NGR could be an agent for tumor vascular-targeting therapy and these findings provided references for further clinical study.

Cited by 1 publication

References 19 publications

Peptide-Mediated Targeting of Cytokines to Tumor Vasculature: The NGR-hTNF Example

Peptide-Mediated Targeting of Cytokines to Tumor Vasculature: The NGR-hTNF Example

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