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Pharmaceutics
Special Issues
Advanced Use of Adenoviral Vectors in Cancer and Gene Therapy
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Advanced Use of Adenoviral Vectors in Cancer and Gene Therapy

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: closed (20 January 2022) | Viewed by 8742

Special Issue Editor

Dr. Dragomira Majhen

E-Mail Website
Guest Editor
Ruđer Bošković Institute, Division of molecular biology, 10 000 Zagreb, Croatia
Interests: adenovirus vectors; targeting; endocytosis; host response
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent decades, we have witnessed major improvements in the therapy of patients with early-stage tumor due to new chemotherapy treatments, refined radiotherapy, and advanced operative techniques. However, serious limitations in classical cancer therapy still exist, and there is a need for innovative therapeutic approaches. Although originally designed as a treatment for monogenetic illness, soon after, gene therapy appeared as a potential new strategy in cancer therapy. The most often used vector for gene transfer in cancer therapy clinical trials is adenovirus. The promising potential of adenoviral vectors is witnessed by the fact that the first-in-class gene therapy product to treat head and neck cancer was adenovirus coding for p53 that entered the commercial market in 2004. Nevertheless, further improvements in vector development technologies are essential to avoid activation of the endogenous signal transduction pathways and production of cytokines due to antivector immune responses that can potentially complicate clinical outcomes. This Special Issue aims to collect the latest advances and state of the art of adenoviral vectors used in cancer and gene therapy. This includes but is not limited to virotherapy, oncolytic vectors, cancer targeting, cancer immune therapy, cancer vaccines, and novel adenoviral vectors that can infect and transduce target cell or tissue with high specificity.

Dr. Dragomira Majhen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cancer therapy
  • Gene therapy
  • Adenoviral vectors
  • Targeting
  • Cancer vaccine
  • Oncolytic adenovirus
  • Virotherapy

Published Papers (3 papers)

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Research

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13 pages, 2109 KiB  
Article
The Feasibility of Pressurised Intraperitoneal Aerosolised Virotherapy (PIPAV) to Administer Oncolytic Adenoviruses
by Sophia J. Tate, Leen Van de Sande, Wim P. Ceelen, Jared Torkington and Alan L. Parker
Pharmaceutics 2021, 13(12), 2043; https://doi.org/10.3390/pharmaceutics13122043 - 30 Nov 2021
Cited by 6 | Viewed by 1834
Abstract
Background: The prognosis of patients with peritoneal metastases is poor. Treatment options are limited because systemically delivered chemotherapy is not usually effective in this type of disease. Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) is a recently developed alternative technology for delivering intraperitoneal chemotherapy, potentially [...] Read more.
Background: The prognosis of patients with peritoneal metastases is poor. Treatment options are limited because systemically delivered chemotherapy is not usually effective in this type of disease. Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) is a recently developed alternative technology for delivering intraperitoneal chemotherapy, potentially enhancing treatment efficacy. Here, we assess the feasibility of pressurised intraperitoneal aerosolised virotherapy (PIPAV) to deliver a different class of anticancer agents, oncolytic adenoviruses, in vitro and in vivo. Methods: Adenoviral vectors expressing reporter genes green fluorescence protein (Ad5.GFP) or firefly luciferase (Ad5.Luc) were subject to pressurised aerosolisation. The ability of the virus to survive PIPAV was assessed in vitro and in vivo by monitoring reporter gene activity. Wistar rats subjected to PIPAV were assessed for any adverse procedure related events. Results: In vitro transduction assays demonstrated that Ad5 retained viability following pressurised aerosolisation and could transduce permissive cells equally effectively as non-aerosolised control vector. PIPAV was well tolerated in rats, although minimal transduction was observed following intraperitoneal administration. Conclusions: PIPAV appears viable and well tolerated, though in vivo efficacy requires further optimisation. Full article
(This article belongs to the Special Issue Advanced Use of Adenoviral Vectors in Cancer and Gene Therapy)
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Review

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17 pages, 13259 KiB  
Review
Adenovirus Type 6: Subtle Structural Distinctions from Adenovirus Type 5 Result in Essential Differences in Properties and Perspectives for Gene Therapy
by Margarita Romanenko, Ivan Osipov, Sergey V. Netesov and Julia Davydova
Pharmaceutics 2021, 13(10), 1641; https://doi.org/10.3390/pharmaceutics13101641 - 08 Oct 2021
Cited by 4 | Viewed by 2512
Abstract
Adenovirus vectors are the most frequently used agents for gene therapy, including oncolytic therapy and vaccine development. It’s hard to overestimate the value of adenoviruses during the COVID-19 pandemic as to date four out of four approved viral vector-based SARS-CoV-2 vaccines are developed [...] Read more.
Adenovirus vectors are the most frequently used agents for gene therapy, including oncolytic therapy and vaccine development. It’s hard to overestimate the value of adenoviruses during the COVID-19 pandemic as to date four out of four approved viral vector-based SARS-CoV-2 vaccines are developed on adenovirus platform. The vast majority of adenoviral vectors are based on the most studied human adenovirus type 5 (HAdV-C5), however, its immunogenicity often hampers the clinical translation of HAdV-C5 vectors. The search of less seroprevalent adenovirus types led to another species C adenovirus, Adenovirus type 6 (HAdV-C6). HAdV-C6 possesses high oncolytic efficacy against multiple cancer types and remarkable ability to induce the immune response towards carrying antigens. Being genetically very close to HAdV-C5, HAdV-C6 differs from HAdV-C5 in structure of the most abundant capsid protein, hexon. This leads to the ability of HAdV-C6 to evade the uptake by Kupffer cells as well as to distinct opsonization by immunoglobulins and other blood proteins, influencing the overall biodistribution of HAdV-C6 after systemic administration. This review describes the structural features of HAdV-C6, its interaction with liver cells and blood factors, summarizes the previous experiences using HAdV-C6, and provides the rationale behind the use of HAdV-C6 for vaccine and anticancer drugs developments. Full article
(This article belongs to the Special Issue Advanced Use of Adenoviral Vectors in Cancer and Gene Therapy)
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18 pages, 1478 KiB  
Review
The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal
by Davor Nestić, Ksenija Božinović, Isabela Pehar, Rebecca Wallace, Alan L. Parker and Dragomira Majhen
Pharmaceutics 2021, 13(10), 1585; https://doi.org/10.3390/pharmaceutics13101585 - 29 Sep 2021
Cited by 13 | Viewed by 3608
Abstract
Adenoviruses represent exceptional candidates for wide-ranging therapeutic applications, from vectors for gene therapy to oncolytics for cancer treatments. The first ever commercial gene therapy medicine was based on a recombinant adenovirus vector, while most recently, adenoviral vectors have proven critical as vaccine platforms [...] Read more.
Adenoviruses represent exceptional candidates for wide-ranging therapeutic applications, from vectors for gene therapy to oncolytics for cancer treatments. The first ever commercial gene therapy medicine was based on a recombinant adenovirus vector, while most recently, adenoviral vectors have proven critical as vaccine platforms in effectively controlling the global coronavirus pandemic. Here, we discuss factors involved in adenovirus cell binding, entry, and trafficking; how they influence efficiency of adenovirus-based vectors; and how they can be manipulated to enhance efficacy of genetically modified adenoviral variants. We focus particularly on endocytosis and how different adenovirus serotypes employ different endocytic pathways to gain cell entry, and thus, have different intracellular trafficking pathways that subsequently trigger different host antiviral responses. In the context of gene therapy, the final goal of the adenovirus vector is to efficiently deliver therapeutic transgenes into the target cell nucleus, thus allowing its functional expression. Aberrant or inefficient endocytosis can impede this goal, therefore, it should be considered when designing and constructing adenovirus-based vectors. Full article
(This article belongs to the Special Issue Advanced Use of Adenoviral Vectors in Cancer and Gene Therapy)
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