Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus

• Main Authors: Ahmed Abdullah Al-Zaher, Rafael Moreno, Carlos Alberto Fajardo, Marcel Arias-Badia, Martí Farrera, Jana de Sostoa, Luis Alfonso Rojas, Ramon Alemany
• Format: Article
• Language: English
• Published: Elsevier 2018-03-01
• Series: Molecular Therapy: Oncolytics
• Online Access: http://www.sciencedirect.com/science/article/pii/S2372770518300032

To enhance adenovirus-mediated oncolysis, different approaches that tackle the selectivity, tumor penetration, and spreading potential of oncolytic adenoviruses have been reported. We have previously demonstrated that insertion of the internalizing Arginine-Glycine-Aspartic (iRGD) tumor-penetrating peptide at the C terminus of the fiber or transgenic expression of a secreted hyaluronidase can improve virus tumor targeting and spreading. Here we report a new oncolytic adenovirus ICOVIR17K-iRGD in which both modifications have been incorporated. In xenografted A549 tumors in nude mice, ICOVIR17K-iRGD shows higher efficacy than the non-iRGD counterpart. To gain insights into the role of the immune system in oncolysis, we have studied ICOVIR17K-iRGD in the tumor isograft mouse model CMT64.6, partially permissive to human adenovirus 5 replication, in immunodeficient or immunocompetent mice. Whereas no efficacy was observed in the immunodeficient setting due to insufficient viral replication, partial efficacy and a polymorphonuclear and CD8+ T cell infiltrate were observed in the immunocompetent mice. The results indicate that the elicitation of a virus-induced anti-tumoral immune response is responsible for the observed partial anti-tumoral effect. Keywords: oncolytic adenovirus, iRGD tumor-penetrating peptide, immune response