Optimizing the Delivery of Anticancer Immune Response-Inducing Oncolytic Adenovirus and Adjuvant Immunotherapeutic
Chae-Ok Yun,
Professor, Department of Bioengineering,
Hanyang University
Currently, intratumoral injection of an oncolytic adenovirus (Ad) remains the conventional administration route in clinical trials. Nonetheless, the locally administered Ad disseminates to the surrounding nontarget tissues and has short biological activity due to immunogenicity of Ad, which inadvertently promotes rapid clearance and insufficient intratumoral retainment of therapeutics. To this end, we developed biocompatible and biodegradable hydrogels to enhance the therapeutic efficacy of oncolytic Ads via single intratumoral administration. A hydrogel-based intratumoral delivery of oncolytic Ads led to prolonged viral retainment within tumor tissues and restricted nonspecific shedding to normal tissues (up to 161.4-fold higher retainment than naked oncolytic Ad). Notably, hydrogel systems attenuated oncolytic Ad-mediated antiviral immune response, which can cause adverse inflammatory response, while preserving the viruses’ ability to induce robust antitumor immune response. One of the hydrogel was capable of efficiently co-delivering and protecting both therapeutic dendritic cells and oncolytic Ad in tumor tissues, thus potentiating the robust antitumor immune response by combination therapy regimen. Collectively, hydrogel-based delivery system enables biological activity of both immunotherapeutic agents could be preserved over a considerable time period in immunosuppressive and hostile tumor microenvironment that significantly diminishes the efficacy of immunotherapeutics. A delivery system, which simultaneously modulates both antiviral and antitumor immune response in a favorable manner to the potency and safety of oncolytic virotherapy in a complex immunological microenvironment of tumors, is of great importance as it may finally enable oncolytic virotherapy to reach its full potential and achieve optimal therapeutic outcome against clinical cancer.
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