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

• Published in: Molecular therapy. Oncolytics Vol. 8; pp. 62 - 70
• Main Authors: Al-Zaher, Ahmed Abdullah, Moreno, Rafael, Fajardo, Carlos Alberto, Arias-Badia, Marcel, Farrera, Martí, de Sostoa, Jana, Rojas, Luis Alfonso, Alemany, Ramon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.03.2018; Elsevier Limited; American Society of Gene & Cell Therapy; Elsevier
• Subjects: Adenoviruses; Arginine; Binding sites; CD8 antigen; Clinical trials; Cytotoxicity; Experiments; Flow cytometry; immune response; Immunodeficiency; Insertion; iRGD tumor-penetrating peptide; Lymphocytes T; Mutation; Oncolysis; oncolytic adenovirus; Peptides; Proteins; Replication; Spreading; Tumors; Viruses; Xenografts; United States > US; Spain; iRGD tumor-penetrating peptide; immune response; oncolytic adenovirus
• ISSN: 2372-7705; 2372-7705
• DOI: 10.1016/j.omto.2018.01.003

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.