Special Issue "Adenoviral Vectors"
Deadline for manuscript submissions: closed (28 February 2014)
Dr. David T. Curiel
Washington University School of Medicine, Department of Radiation Oncology, 4511 Forest Park, St. Louis, MO 63108, USA
Phone: +1 314 362 9789
Fax: +1 314 362 9797
Interests: adenovirus; virotherapy; gene therapy
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Review: Peptide-Based Technologies to Alter Adenoviral Vector Tropism: Ways and Means for Systemic Treatment of Cancer
Viruses 2014, 6(4), 1540-1563; doi:10.3390/v6041540
Received: 10 February 2014; in revised form: 15 March 2014 / Accepted: 20 March 2014 / Published: 2 April 2014| Download PDF Full-text (647 KB) | Download XML Full-text
Viruses 2014, 6(2), 832-855; doi:10.3390/v6020832
Received: 18 December 2013; in revised form: 10 February 2014 / Accepted: 11 February 2014 / Published: 17 February 2014| Download PDF Full-text (933 KB) | View HTML Full-text | Download XML Full-text
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Review
Title: Peptide-Based Technologies to Alter Adenoviral Vector Tropism: Ways and Means to Treat Systemic Disease
Authors: Brigitte Pützer, Ottmar Herchenröder et al.
Affiliation: Rostock University Medical Center, Institute of Experimental Gene Therapy and Cancer Research, Schillingallee 69, D-18057 Rostock, Germany
Abstract: Due to the fundamental progress in elucidating the molecular mechanisms of human diseases and the arrival of the post-genomic era, increasing numbers of therapeutic genes and targets are available for gene therapy. Meanwhile, the most important challenge is to develop gene delivery vectors with high efficiency through target cell selectivity in particular under in situ conditions. The widely used vector system to transduce cells is based on adenovirus (Ad). Recent endeavors in the development of selective Ad vectors that target cells or tissues of interest and spare alteration of all others have focused on the modification of the virus broad natural tropism. A popular way of Ad targeting is by directing the vector towards distinct cellular receptors. Redirecting can be achieved by linking custom-made peptides with specific affinity to cellular surface proteins via genetic integration, chemical coupling, or bridging with dual-specific adapter molecules. Ideally, targeted vectors are incapable of entering cells via their native receptors. Such altered vectors not only offer new opportunities to delineate functional genomics in a natural environment but may also enable efficient therapy of systemic diseases. This review provides a summary of current state-of-the-art techniques to specifically target adenovirus-based gene delivery vectors.
Type of Paper: Article
Title: Effective Transfer of the Oncolytic Adenoviral Vector Delta24-RGD by a T-cell Derived Cellular Vehicle System in Vivo
Authors: Rutger K. Balvers 1, Sanne K. van den Hengel 2, Hiroaki Wakimoto 3, Rob C. Hoeben 2, Reno Debets 4, Sieger Leenstra 1, Clemens Dirven 1 and Martine L.M. Lamfers 1
Affiliations: 1 Dept of Neurosurgery, Brain Tumor Center, Erasmus MC, Rotterdam, Netherlands; Dr. Molewaterplein 50, Ee2236, 3015GE, Rotterdam, The Netherlands
2 Department of Molecular Cell Biology, LUMC Leiden, The Netherlands
3 Molecular Neurosurgery Laboratory, Brain Tumor Research Center, Massachusetts General Hospital, Boston, USA
4 Laboratory of Experimental Tumor Immunology, Department Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands; Corresponding author: Martine Lamfers, Department of Neurosurgery, Erasmus MC Rotterdam, firstname.lastname@example.org
Short Title: Carrier cell mediated delivery of Delta24-RGD in invasive GBM
Abstract: Oncolytic adenoviral vectors are a promising alternative for the treatment of glioblastoma. Recent publications have demonstrated the advantages of shielding viral particles within cellular vehicles (CVs), which can be targeted towards the tumor microenvironment. We investigated the feasibility of using a T-cell derived CV system to deliver the oncolytic adenovirus Delta24-RGD to glioblastoma.
The T-cell derived cell line Jurkat was assessed in co-culture with the glioblastoma stem cell line GBM8 for optimal transfer conditions of Delta24-RGD in vitro. The effect of intraparenchymal and tail-vein injections on intratumoral viral distribution and overall survival was addressed in an orthotopic GSC based xenograft model.
Jurkats were demonstrated to facilitate Delta24-RGD amplification and transfer to GSC’s. Delta24-RGD dosing and incubation time were found to influence the migratory ability of Jurkats towards GSC’s. Injection of Delta24-RGD-loaded Jurkats into the brains of GBM8-bearing mice led to Jurkat migration towards the tumor and dispersion of the virus within its core and infiltrative zones. This occurred after injection into the ipsi-lateral hemisphere as well as into the contralateral hemisphere. We found that Jurkat-mediated delivery of Delta24RGD led to inhibition of tumor growth compared to controls, resulting in prolonged survival compared to controls (46 days versus 38 days, p=0.007). However, tail-vein injections failed to demonstrate intraparenchymal Jurkat or viral delivery.
Based on these findings we conclude that T-cell based CV’s are a feasible candidate for Delta24-RGD delivery in glioblastoma, although efficient systemic targeting needs further evaluation.
Keywords: Glioblastoma; Oncolytic; Cellular Vehicles; GSC; Virotherapy; Delta24-RGD
Type of Paper: Article
Title: Transient Immunosuppression in Adenoviral-sensitized Cirrhotic Rats Reduces Liver Necroinflammation and Does not Affect Adenovector Biodistribution
Authors: Ana Sandoval-Rodríguez 1, Mayra Mena-Enriquez 1, Jesus Garcia-Bañuelos 1, Adriana Salazar-Montes 1, Mary Fafutis-Morris 3 and Juan Armendariz-Borunda 1,2
1 Institute for Molecular Biology and Gene Therapy, Department of Molecular Biology and Genomics, University of Guadalajara, Guadalajara, Jalisco, Mexico
2 INNOVARE, Guadalajara, Jalisco, Mexico
3 Research Center for Immunology and Dermatology, Department of Physiology, University of Guadalajara, Mexico; Address correspondence to: Dr. Juan Armendariz-Borunda, Sierra Mojada 950, Colonia Independencia, Guadalajara, Jalisco 44340, Mexico; E-mail: email@example.com; Phone +52 (33) 10585317; Fax: +52 (33) 10585318
Running Title: Ad-distribution in Immunosuppressed Cirrhotic Rats
Abstract: The use of Adenoviruses (Ad) as gene therapy vectors has rendered sensitization in humans, which precludes re-administration possibilities. In the past, our group used a single injection of Ad-hΔuPA as a gene vector and demonstrated its effectiveness as an antifibrotic therapy in several experimental cirrhosis models. As a further approach in humans, transient Cyclosporine A (CsA) immunosuppression was induced in cirrhotic animals to achieve temporary immunosuppression and determine whether an Ad-hΔuPA administration retained efficacy. Adenovirus sensitization was achieved by systemic administration of non-therapeutic Ad-Gal after 4 weeks of intraperitoneal CCl4 regimen and the process of cirrhosis induction was continued up to 8 weeks. At the end of the CCl4 intoxication, immunosuppression was achieved administrating three different times 40mg/kg of CsA: 24 h before administration of Ad-hΔuPA, at the moment of Ad-huPA dose and finally 24 h after Ad-hΔuPA injection. At 2 and 72 hours after the administration of Ad-hΔuPA, animals were sacrificed. Then the liver, spleen, lung, kidney, heart, brain and testis were analyzed for Ad biodistribution and transgene expression. In naïve animals, Ad-hΔuPA genomes prevailed in liver and spleen, while Ad-sensitized rats showed Ad genomes also in kidney and heart. Cirrhosis and Ad-preimmunization status diminished notably transgene liver-expression compared to healthy-livers. CsA immunosuppression diminished liver necroinflammation and cell infiltration, with no effect on the Ad-hΔuPA biodistribution. Importantly, an increment in animal survival was noted in these immunosuppressed animals.
Type of Paper: Review
Title: The Evolution of Adenoviral Vectors from Genetic to Chemical Surface-modifications
Authors: Cristian Capasso 1, Mariangela Garofalo 2, Mari Hirvinen 1 and Vincenzo Cerullo 1,*
Affiliations: 1 Laboratory of Immunovirotherapy; Division of Biopharmaceutics and Pharmacokinetics; Faculty of Pharmacy; University of Helsinki; Helsinki, Finland
2 Dipartimento di Biologia, Italy
Abstract: Many years have passed since the first clinical trials with adenoviral vectors. Despite being very promising, gene therapy approaches revealed their limitations for human therapies. Pre-existing immunity, poor transduction efficacy and high toxicity of first viral vectors have been the main challenges for novel approaches. In the last decades, researchers tried to address these issues by engineering viral vectors to reduce their immunogenicity, to enhance the delivery, to increase the expression of the transgene and to control the tropism of the vectors. Much effort has been invested in the development of genetic, chemical and non-chemical modifications of adenoviral vectors allowing researchers to built better gene therapy vectors characterized by an improved safety profile, along with higher transduction ability. In this review we will describe latest findings in the high-speed evolving field of genetic and surface modification of adenoviral vectors, a field where different disciplines, such as biomaterial research, virology and immunology co-operate synergistically to create better gene therapy tools for modern challenges.
Last update: 3 February 2014