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Published on: August 23, 2019
Antitumor Activity of VB-111, a Novel Antiangiogenic Virotherapeutic, in Thyroid Cancer Xenograft Mouse Models
H V Reddi1, P Madde, Y C Cohen
1Department of Medicine, Division of Endocrinology, Mayo Clinic, Rochester, MN, USA.
Abstract:
VB-111 is an engineered antiangiogenic adenovirus that expresses Fas-c in angiogenic blood vessels and has previously been shown to have significant antitumor activity in vitro and in vivo in Lewis lung carcinoma, melanoma, and glioblastoma models. To evaluate the efficacy of VB-111 in thyroid cancer, we conducted in vivo xenograft nude mouse studies using multiple thyroid cancer-derived cell lines models. VB-111 treatment resulted in 26.6% (P = 0.0596), 34.4% (P = 0.0046), and 37.6% (P = 0.0249) inhibition of tumor growth in follicular, papillary and anaplastic thyroid cancer models, respectively. No toxicity was observed in any model. All tumor types showed a consistent and significant reduction of CD-31 staining (P < 0.05), reflecting a reduction of angiogenic activity in the tumors, consistent with the intended targeting of the virus. A phase 2 clinical trial of VB-111 in patients with advanced differentiated thyroid cancer is ongoing.
Insights
VB-111, an antiangiogenic adenovirus, effectively inhibited thyroid cancer growth in preclinical models without toxicity. This suggests VB-111
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- VB-111 is an engineered adenovirus designed for antiangiogenic therapy.
- It expresses Fas-c in tumor vasculature, demonstrating antitumor effects in various cancer models.
- Its potential in thyroid cancer treatment requires further investigation.
Purpose of the Study:
- To evaluate the efficacy of VB-111 in preclinical thyroid cancer models.
- To assess VB-111's impact on tumor growth and angiogenesis in different thyroid cancer subtypes.
Main Methods:
- In vivo xenograft studies were performed in nude mice using multiple thyroid cancer cell lines.
- Tumor growth inhibition was measured following VB-111 treatment.
- CD-31 staining was used to assess changes in tumor angiogenesis.
Main Results:
- VB-111 treatment significantly inhibited tumor growth in follicular (26.6%), papillary (34.4%), and anaplastic (37.6%) thyroid cancer models.
- A significant reduction in CD-31 staining indicated decreased angiogenic activity across all tested tumor types.
- No observable toxicity was reported in any of the tested models.
Conclusions:
- VB-111 demonstrates significant anti-tumor and anti-angiogenic efficacy in preclinical thyroid cancer models.
- The findings support the ongoing clinical evaluation of VB-111 for advanced differentiated thyroid cancer.
