Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-03-01
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| Series: | Molecular Therapy: Oncolytics |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770518300032 |
| _version_ | 1811212607038685184 |
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| author | Ahmed Abdullah Al-Zaher Rafael Moreno Carlos Alberto Fajardo Marcel Arias-Badia Martí Farrera Jana de Sostoa Luis Alfonso Rojas Ramon Alemany |
| author_facet | Ahmed Abdullah Al-Zaher Rafael Moreno Carlos Alberto Fajardo Marcel Arias-Badia Martí Farrera Jana de Sostoa Luis Alfonso Rojas Ramon Alemany |
| author_sort | Ahmed Abdullah Al-Zaher |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-04-12T05:31:55Z |
| format | Article |
| id | doaj.art-0a2e8c7b9ae940cbaf08ac217ac2324d |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-04-12T05:31:55Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-0a2e8c7b9ae940cbaf08ac217ac2324d2022-12-22T03:46:01ZengElsevierMolecular Therapy: Oncolytics2372-77052018-03-0186270Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic AdenovirusAhmed Abdullah Al-Zaher0Rafael Moreno1Carlos Alberto Fajardo2Marcel Arias-Badia3Martí Farrera4Jana de Sostoa5Luis Alfonso Rojas6Ramon Alemany7ProCure Program, IDIBELL-Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainProCure Program, IDIBELL-Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainProCure Program, IDIBELL-Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainProCure Program, IDIBELL-Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainProCure Program, IDIBELL-Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainProCure Program, IDIBELL-Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainProCure Program, IDIBELL-Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainProCure Program, IDIBELL-Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain; Corresponding author: Ramon Alemany, IDIBELL-Institut Català d’Oncologia, Av. Gran Via de l’Hospitalet 199-203, L’Hospitalet de Llobregat, 08907 Barcelona, Spain.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 responsehttp://www.sciencedirect.com/science/article/pii/S2372770518300032 |
| spellingShingle | Ahmed Abdullah Al-Zaher Rafael Moreno Carlos Alberto Fajardo Marcel Arias-Badia Martí Farrera Jana de Sostoa Luis Alfonso Rojas Ramon Alemany Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus Molecular Therapy: Oncolytics |
| title | Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus |
| title_full | Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus |
| title_fullStr | Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus |
| title_full_unstemmed | Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus |
| title_short | Evidence of Anti-tumoral Efficacy in an Immune Competent Setting with an iRGD-Modified Hyaluronidase-Armed Oncolytic Adenovirus |
| title_sort | evidence of anti tumoral efficacy in an immune competent setting with an irgd modified hyaluronidase armed oncolytic adenovirus |
| url | http://www.sciencedirect.com/science/article/pii/S2372770518300032 |
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