Oncolytic Adenoviruses in Cancer Treatment

Abstract

The therapeutic use of viruses against cancer has been revived during the last two decades. Oncolytic viruses replicate and spread inside tumors, amplifying their cytotoxicity and simultaneously reversing the tumor immune suppression. Among different viruses, recombinant adenoviruses designed to replicate selectively in tumor cells have been clinically tested by intratumoral or systemic administration. Limited efficacy has been associated to poor tumor targeting, intratumoral spread, and virocentric immune responses. A deeper understanding of these three barriers will be required to design more effective oncolytic adenoviruses that, alone or combined with chemotherapy or immunotherapy, may become tools for oncologists.

Keywords: adenovirus; cancer; oncolytic; virotherapy.

Figure 1

Obstacles to overcome in adenovirus-mediated virotherapy. In blood the Ad capsid binds to erythrocytes, platetes, monocytes, neutrophils, antibodies, complement, and clotting factors. In liver, the capsid binds to Kupffer cells and hepatocytes. In tumors, the diffusion of the virus is blocked by the stroma formed by an extracellular matrix and cells such as cancer-associated fibroblasts. An innate inflammatory response calls antigen presenting cells to the tumor site to capture and transport antigens to lymph nodes to elicit an adaptive responses dominated by the virus.