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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Peptide-mediated targeting of cytokines to tumor vasculature: the NGR-hTNF example

Angelo Corti1, Flavio Curnis, Gilda Rossoni

  • 1Tumor Biology and Vascular Targeting Unit, Division of Molecular Oncology, San Raffaele Scientific Institute, via Olgettina 58, 20132, Milan, Italy, corti.angelo@hsr.it.

Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
|June 8, 2013
PubMed

Insights

Targeting tumor vasculature with peptide-cytokine conjugates enhances cancer therapy. This approach allows low, effective doses of cytokines (like tumor necrosis factor-α) without triggering adverse systemic responses.

Area of Science:

  • Oncology
  • Biotechnology
  • Molecular Biology

Background:

  • Cytokine therapy efficacy in cancer is limited by systemic toxicity and counter-regulatory mechanisms.
  • Targeting strategies aim to deliver therapeutic agents specifically to tumor cells or the tumor microenvironment.
  • Tumor vasculature presents a unique target for drug delivery, distinct from tumor cells themselves.

Purpose of the Study:

  • To review the use of tumor vasculature-homing peptides for targeted delivery of cytokines in cancer therapy.
  • To explore peptide-cytokine conjugates utilizing NGR, RGD, isoDGR, or RGR peptide sequences.
  • To detail the properties of NGR-human tumor necrosis factor-α (NGR-hTNF) conjugates in clinical development.

Main Methods:

  • Conjugation of cytokines with tumor vasculature-homing peptides.
  • Evaluation of peptide-cytokine conjugates in preclinical cancer models.
  • Analysis of clinical trial data for NGR-hTNF conjugates in phase II and III studies.

Main Results:

  • Peptide-mediated vascular-targeting enables delivery of bioactive cytokines to tumor endothelial cells.
  • Targeted delivery allows for administration of extremely low cytokine doses, avoiding systemic toxicity.
  • NGR-hTNF conjugates have shown promise in preclinical and clinical studies, demonstrating efficacy without significant adverse effects.

Conclusions:

  • Peptide-cytokine conjugates targeting tumor vasculature represent a viable strategy for cancer treatment.
  • This approach effectively delivers therapeutic cytokines while mitigating systemic counter-regulatory responses and toxicity.
  • Further clinical development of agents like NGR-hTNF is warranted for improved cancer therapy.

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