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VB-111 for cancer
Pierre L Triozzi1, Ernest C Borden
1Taussig Cancer Institute, Cleveland, OH 44195, USA. triozzp@ccf.org
Introduction:
Antibody, small molecule and protein inhibitors of angiogenesis are used in the management of several cancers. These do not specifically target tumor vascularity, and resistance can be problematic. VB-111 is a vascular-targeting agent consisting of a non-replicating adenovirus vector with a pre-proendothelin-1 promoter that encodes an apoptotic receptor.
Areas Covered:
The rationale and design of VB-111, its mechanism of action, and preclinical studies examining antitumor activity, toxicology and pharmacodynamics are reviewed. Phase I and Phase II clinical trials are also reviewed.
Expert Opinion:
VB-111 is a vascular-targeting gene therapeutic that is both tissue- and condition-specific, with effects limited to endothelial cells undergoing angiogenesis. Systemic administration produces selective destruction of tumor vascularity. Synergistic antitumor activity can be observed when combined with chemotherapy. VB-111 has been found to be safe and well tolerated in a Phase I clinical trial in patients with advanced solid tumors. Phase II clinical trials are in progress. VB-111 is novel agent for cancer that may have application as monotherapy and in combination with other therapies.
Insights
VB-111, a novel gene therapy, selectively targets tumor blood vessels by inducing endothelial cell apoptosis. This vascular-targeting agent shows promise as a cancer monotherapy or in combination with chemotherapy, with early trials demonstrating safety and tolerability.
Area of Science:
- Oncology
- Gene Therapy
- Vascular Biology
Background:
- Current anti-angiogenesis therapies for cancer face challenges with specificity and resistance.
- VB-111 represents a novel approach to cancer treatment by targeting tumor vascularity.
Purpose of the Study:
- To review the rationale, design, and mechanism of action of VB-111.
- To summarize preclinical and clinical trial data for VB-111.
Main Methods:
- Review of VB-111's design: a non-replicating adenovirus vector encoding an apoptotic receptor under a pre-proendothelin-1 promoter.
- Examination of preclinical studies on antitumor activity, toxicology, and pharmacodynamics.
- Review of Phase I and Phase II clinical trial data.
Main Results:
- VB-111 demonstrates tissue- and condition-specific targeting of angiogenic endothelial cells.
- Systemic administration leads to selective destruction of tumor vasculature.
- Preclinical studies indicate potential for synergistic antitumor activity with chemotherapy.
Conclusions:
- VB-111 is a novel vascular-targeting gene therapeutic with specific effects on tumor angiogenesis.
- Early clinical trials (Phase I) indicate VB-111 is safe and well-tolerated in patients with advanced solid tumors.
- Ongoing Phase II trials will further evaluate VB-111's efficacy as a monotherapy and in combination regimens for cancer treatment.
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