Oncolytic Adenovirus: Prospects for Cancer Immunotherapy

Immunotherapy has moved to the forefront of modern oncologic treatment in the past few decades. Various forms of immunotherapy currently are emerging, including oncolytic viruses. In this therapy, viruses are engineered to selectively propagate in tumor cells and reduce toxicity for non-neoplastic tissues. Adenovirus is one of the most frequently employed oncolytic viruses because of its capacity in tumor cell lysis and immune response stimulation. Upregulation of immunostimulatory signals induced by oncolytic adenoviruses (OAds) might significantly remove local immune suppression and amplify antitumor immune responses. Existing genetic engineering technology allows us to design OAds with increasingly better tumor tropism, selectivity, and antitumor efficacy. Several promising strategies to modify the genome of OAds have been applied: capsid modifications, small deletions in the pivotal viral genes, insertion of tumor-specific promoters, and addition of immunostimulatory transgenes. OAds armed with tumor-associated antigen (TAA) transgenes as cancer vaccines provide additional therapeutic strategies to trigger tumor-specific immunity. Furthermore, the combination of OAds and immune checkpoint inhibitors (ICIs) increases clinical benefit as evidence shown in completed and ongoing clinical trials, especially in the combination of OAds with antiprogrammed death 1/programed death ligand 1 (PD-1/PD-L1) therapy. Despite remarkable antitumor potency, oncolytic adenovirus immunotherapy is confronted with tough challenges such as antiviral immune response and obstruction of tumor microenvironment (TME). In this review, we focus on genomic modification strategies of oncolytic adenoviruses and applications of OAds in cancer immunotherapy.