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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Oncolytic virus delivery: from nano-pharmacodynamics to enhanced oncolytic effect
Raquel Yokoda1, Bolni M Nagalo1, Brent Vernon2
1Division of Hematology Oncology, Department of Medicine, Mayo Clinic, Scottsdale.
Abstract:
With the advancement of a growing number of oncolytic viruses (OVs) to clinical development, drug delivery is becoming an important barrier to overcome for optimal therapeutic benefits. Host immunity, tumor microenvironment and abnormal vascularity contribute to inefficient vector delivery. A number of novel approaches for enhanced OV delivery are under evaluation, including use of nanoparticles, immunomodulatory agents and complex viral-particle ligands along with manipulations of the tumor microenvironment. This field of OV delivery has quickly evolved to bioengineering of complex nanoparticles that could be deposited within the tumor using minimal invasive image-guided delivery. Some of the strategies include ultrasound (US)-mediated cavitation-enhanced extravasation, magnetic viral complexes delivery, image-guided infusions with focused US and targeting photodynamic virotherapy. In addition, strategies that modulate tumor microenvironment to decrease extracellular matrix deposition and increase viral propagation are being used to improve tumor penetration by OVs. Some involve modification of the viral genome to enhance their tumoral penetration potential. Here, we highlight the barriers to oncolytic viral delivery, and discuss the challenges to improving it and the perspectives of establishing new modes of active delivery to achieve enhanced oncolytic effects.
Insights
Oncolytic virus (OV) delivery faces challenges from immunity and the tumor environment. Novel strategies like nanoparticles and image-guided methods aim to improve OV delivery for enhanced cancer treatment.
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Oncolytic viruses (OVs) show promise in cancer therapy but face significant delivery barriers.
- Host immunity, the tumor microenvironment (TME), and abnormal tumor vascularity impede efficient OV vector delivery.
- Overcoming these barriers is crucial for maximizing the therapeutic potential of OVs.
Purpose of the Study:
- To review the key barriers hindering effective oncolytic virus delivery.
- To discuss current and emerging strategies for enhancing OV delivery and tumor penetration.
- To explore future perspectives in active delivery methods for improved oncolytic effects.
Main Methods:
- Review of novel approaches for enhanced OV delivery, including nanoparticles, immunomodulatory agents, and viral-particle ligands.
- Discussion of TME modulation strategies to improve viral propagation and penetration.
- Highlighting advanced delivery techniques such as ultrasound-mediated delivery, magnetic targeting, and photodynamic virotherapy.
- Consideration of viral genome modifications to enhance tumoral penetration.
Main Results:
- Several innovative strategies are being evaluated to improve OV delivery, including bioengineered nanoparticles and image-guided delivery systems.
- Techniques like ultrasound-mediated cavitation, magnetic viral complexes, and focused ultrasound infusions show potential for enhanced extravasation and targeted delivery.
- TME modulation and viral genome engineering are actively being pursued to improve tumor penetration and viral efficacy.
Conclusions:
- Effective delivery remains a critical challenge for oncolytic virus therapy.
- A combination of bioengineering, advanced delivery techniques, and TME manipulation is essential for optimizing OV efficacy.
- Future research should focus on developing robust active delivery systems to achieve superior oncolytic effects.
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