Achieving systemic delivery of oncolytic viruses

Abstract

Introduction: Oncolytic virotherapy is a selective and powerful tool for cancer treatment. Studies proving the ability of oncolytic viruses (OVs) to target and rapidly kill cancer cells have led to approval of H101 and Imlygic®. Both these OVs are restricted to intratumoral administration into cancer lesions. Despite promising preclinical results, systemic delivery of OV has shown limited success in patients due to a knockdown in infectivity, as a result of rapid immune-mediated neutralization, and poor penetration into tumors. Areas covered: This review catalogs the techniques used to enhance OV delivery. Firstly, insights from clinical trials of OV provide evidence of the need for enhanced delivery strategies. Secondly, the techniques applied to overcome the challenges highlighted by clinical trial data (i.e. suboptimal pharmacokinetics, antiviral immune responses, and poor penetration into solid tumors) are reviewed. Expert opinion: For OV to gain traction and convert potential into value, researchers focussed on showing clinical and commercial viability following intratumoral injection. For the technology to mature and become applicable across a wider range of patients/cancer indications, amenability to systemic delivery is required. This may be achieved using strategies that modulate the OV by genetic or chemical means and/or that alter the physiology of target tumors. ARTICLE HISTORY

Oncolytic Viruses for Cancer Therapy: Barriers and Recent Advances

“…These are different kinds of strategies for the delivery of OVs because they are noninvasive and have been used for many years in the biomedical imaging field. What is more, magnetic drug-targeted viruses are able to pass through human tissues without attenuation 47 …”

Clinical Application of Oncolytic Viruses: A Systematic Review

“…However many trials are also evaluating intravenous route of administration [ 44 , 45 ] due to its inherent advantages. Some of the advantages of IV route includes ease of administration, standardization of administered drug dose, potential for multiple and long term administration, and wider application of IV based treatment especially in smaller community clinics [ 46 ]. The key detriment to IV administration so far has been development of neutralizing antibodies and clearance of OV [ 47 , 48 , 49 ].…”

Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions

“…Unfortunately, although treatment effects were observed in vitro and in vivo studies [121,122], this intrabody therapy did not achieve significant clinical efficacy [123]. The lack of treatment efficacy could be partially associated with the unclear PK/PD profiles [124][125][126]. For instance, the pre-existing immune response against adenovirus could influence the PK/PD profiles of the gene therapies with adenoviral vectors and diminish transgene expression efficiency [127].…”