Oncolytic virus delivery: from nano-pharmacodynamics to enhanced oncolytic effect

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.

Delivery of cancer therapies by synthetic and bio-inspired nanovectors

“…Despite pre-existing immunity having no measurable effect on the therapeutic outcome after intratumoral injection, innate and adaptive immune responses against circulating viruses may restrict their efficacy after intravenous administration [104,105]. PEGylation of OVs [106,107] or switching OV species during the course of treatment [108,109] can improve stealthiness and enhance treatment efficacy. Enveloped viruses can also be pseudotyped with different viral envelops [110][111][112], while changing the serotype of non-enveloped viruses could evade the immune response [113][114][115].…”

Clinical Application of Oncolytic Viruses: A Systematic Review

“…Vascular injection also has limitations. Tumor vasculature is markedly disorganized and more unstable than normal vessels [ 41 ]; this property makes vascular injections less reliable for downstream delivery of the virus to surrounding cancer cells. However, currently there are several avenues under investigation to stabilize these tissues and enhance delivery of cancer immunotherapy; some examples include the use of nitric oxide [ 42 ] and VEGF [ 43 ].…”

Repurposing Infectious Pathogen Vaccines in Cancer Immunotherapy

“…Entire pathogens, in particular recombinant oncolytic viruses, have been engineered to sustain selective replication into malignant cells [46,47]. However, experience with the use of these oncolytic viruses, originally thought as cytolytic agents, has shown that antitumor immune response against viral-infected cells is a fundamental factor for their anticancer efficacy [48]. Therefore, modern viral vectors are genetically engineered to also express cytokines and other immune stimulating factors [49].…”