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Light-enhanced VEGF

Anette Weyergang1, Ane S Fremstedal1, Ellen Skarpen2

  • 1Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University hospital, Norway.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|September 16, 2018
PubMed
Summary
This summary is machine-generated.

Vascular targeted fusion toxin VEGF121/rGel combined with photochemical internalization (PCI) effectively targets cancer cells and tumor vasculature. This combination therapy shows promise for multimodal cancer treatment, including complete remission in colon carcinoma models.

Keywords:
Immune mediated cell deathPhotochemical internalizationTargeted toxinVEGFRVascular targeting

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Area of Science:

  • Oncology
  • Cancer Biology
  • Drug Delivery Systems

Background:

  • Tumor-stroma interactions significantly influence cancer progression.
  • Current drug regimens target cancer cells and stroma, but adverse effects limit efficacy.
  • Novel, tolerable treatments with high efficacy against both tumor and stromal cells are needed.

Purpose of the Study:

  • To investigate the anticancer mechanisms of vascular targeted fusion toxin VEGF121/rGel combined with photochemical internalization (PCI).
  • To evaluate the efficacy of VEGF121/rGel-PCI in inhibiting tumor perfusion and inducing cancer cell death.
  • To determine the role of immune-mediated responses in the treatment outcome.

Main Methods:

  • VEGF121/rGel-PCI treatment was administered to tumor models.
  • VEGF receptor expression (VEGFR1, VEGFR2) was analyzed.
  • Tumor perfusion was assessed using dynamic contrast-enhanced MRI.
  • Treatment efficacy was evaluated in immunocompetent and athymic mice.

Main Results:

  • VEGF121/rGel-PCI, unlike monotherapy, targeted VEGFR1 and VEGFR2, affecting VEGFR1-expressing cancer cell lines.
  • Histological analysis indicated direct cancer parenchymal cell death.
  • Sustained inhibition of tumor perfusion was observed via MRI.
  • Complete remission was achieved in 50% of CT26.CL25 colon carcinoma models in immunocompetent mice, but not in athymic mice.

Conclusions:

  • VEGF121/rGel-PCI demonstrates multimodal tumor-targeted efficacy.
  • The treatment's effectiveness is partly mediated by immune responses.
  • VEGF121/rGel-PCI warrants further development for clinical application.