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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Anti-metastatic activity of the tumor vascular targeting agent NGR-TNF
Paola Di Matteo1, Patrizia Mangia, Elena Tiziano
1MolMed SpA, via Olgettina 58, 20132, Milan, Italy.
Abstract:
Tumor vessels are an attractive target for cancer therapy, including metastasis treatment. Angiogenesis inhibitors targeting the VEGF signalling pathway have proven to be efficacious in preclinical cancer models and in clinical trials. However, angiogenesis inhibition concomitantly elicits tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased distant metastasis. Here, we investigated whether NGR-TNF, a vascular targeting agent in phase III clinical development, coupling the CNGRCG angiogenic vessel-homing peptide with TNF-α, has an effect on metastasis in a model of murine breast cancer, which spontaneously metastasize to lungs, and on the growth of experimental melanoma lung metastasis. We report that NGR-TNF does not increase cancer invasiveness, as other antiangiogenics agents do, but controls metastatic growth in both models, both when administered as primary treatment and in adjuvant settings, improving the overall survival of metastasis-bearing mice.
Insights
NGR-TNF, a novel vascular targeting agent, effectively controls metastatic growth in breast and melanoma cancer models without increasing invasiveness. This treatment improves survival in mice with metastasis.
Area of Science:
- Oncology
- Cancer Biology
- Vascular Biology
Background:
- Tumor vasculature is a key target for cancer therapies, including metastasis treatment.
- Anti-angiogenic agents targeting VEGF signaling show efficacy but can promote tumor invasiveness and metastasis.
- Tumor adaptation to anti-angiogenesis can lead to more aggressive cancer phenotypes.
Purpose of the Study:
- To investigate the effect of NGR-TNF on spontaneous and experimental lung metastasis in murine breast cancer and melanoma models.
- To determine if NGR-TNF exacerbates cancer invasiveness, unlike other anti-angiogenic agents.
- To evaluate NGR-TNF's efficacy as a primary and adjuvant treatment for metastatic disease.
Main Methods:
- Utilized a murine breast cancer model with spontaneous lung metastasis.
- Employed an experimental melanoma lung metastasis model.
- Administered NGR-TNF as both primary and adjuvant therapy.
- Assessed cancer invasiveness, metastatic growth, and overall survival.
Main Results:
- NGR-TNF did not increase cancer invasiveness in either model.
- NGR-TNF effectively controlled metastatic growth in both spontaneous and experimental lung metastasis models.
- Treatment with NGR-TNF, as primary or adjuvant therapy, improved overall survival in metastasis-bearing mice.
Conclusions:
- NGR-TNF represents a promising vascular-targeting agent for controlling cancer metastasis.
- Unlike other anti-angiogenic therapies, NGR-TNF does not appear to promote cancer invasiveness.
- NGR-TNF demonstrates therapeutic potential in improving survival outcomes for metastatic cancer patients.
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