Current Use of Adenovirus Vectors and Their Production Methods

Sayedahmed, Ekramy E.; Kumari, Rashmi; Mittal, Suresh K.

doi:10.1007/978-1-4939-9065-8_9

Cited by 24 publications

(17 citation statements)

References 77 publications

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“… 4 5 A sophisticated form of immunotherapy is represented by oncolytic viruses: thanks to an increased knowledge of the molecular and biological characteristics of some pathogenic viruses and of the host immune response, it has become possible to engineer viruses in order to turn them into anticancer drugs. Adenoviruses (Ads)have been largely studied both as gene therapy vectors 6 to transfer genes in mammalian cells, or as oncolytic adenoviruses (OAs), genetically engineered to selectively replicate in and lyse tumor cells, sparing normal tissues. 7 8 In preclinical studies, OA showed very promising results 9–11 ; however, the clinical translation did not reach a comparable efficacy.…”

Section: Introductionmentioning

confidence: 99%

Oncolytic adenovirus and gene therapy with EphA2-BiTE for the treatment of pediatric high-grade gliomas

Arnone

Polito

Mastronuzzi

et al. 2021

J Immunother Cancer

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BackgroundPediatric high-grade gliomas (pHGGs) are among the most common and incurable malignant neoplasms of childhood. Despite aggressive, multimodal treatment, the outcome of children with high-grade gliomas has not significantly improved over the past decades, prompting the development of innovative approaches.MethodsTo develop an effective treatment, we aimed at improving the suboptimal antitumor efficacy of oncolytic adenoviruses (OAs) by testing the combination with a gene-therapy approach using a bispecific T-cell engager (BiTE) directed towards the erythropoietin-producing human hepatocellular carcinoma A2 receptor (EphA2), conveyed by a replication-incompetent adenoviral vector (EphA2 adenovirus (EAd)). The combinatorial approach was tested in vitro, in vivo and thoroughly characterized at a molecular level.ResultsAfter confirming the relevance of EphA2 as target in pHGGs, documenting a significant correlation with worse clinical outcome of the patients, we showed that the proposed strategy provides significant EphA2-BiTE amplification and enhanced tumor cell apoptosis, on coculture with T cells. Moreover, T-cell activation through an agonistic anti-CD28 antibody further increased the activation/proliferation profiles and functional response against infected tumor cells, inducing eradication of highly resistant, primary pHGG cells. The gene-expression analysis of tumor cells and T cells, after coculture, revealed the importance of both EphA2-BiTE and costimulation in the proposed system. These in vitro observations translated into significant tumor control in vivo, in both subcutaneous and a more challenging orthotopic model.ConclusionsThe combination of OA and EphA2-BiTE gene therapy strongly enhances the antitumor activity of OA, inducing the eradication of highly resistant tumor cells, thus supporting the clinical translation of the approach.

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Section: Introductionmentioning

confidence: 99%

Oncolytic adenovirus and gene therapy with EphA2-BiTE for the treatment of pediatric high-grade gliomas

Arnone

Polito

Mastronuzzi

et al. 2021

J Immunother Cancer

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“…For developing HAdv vectors Article ll expressing the Ag85B-p25 epitope of Mtb without (HAdv85) or with AIP-C5 (HAdv 85C5 ) (Figure 1), we applied the technology of Cre recombinase-mediated homologous recombination. 100 The gene cassette in BAdv or HAdv vectors was under the control of the cytomegalovirus (CMV) immediate early promoter and the bovine growth hormone (BGH) polyadenylation signal. The presence of the foreign gene cassette in the vector was identified initially by restriction analysis followed by sequencing the region containing the gene cassette.…”

Section: Bacterial Strains and Culture Conditionsmentioning

confidence: 99%

A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice

Khan

Sayedahmed

Singh

et al. 2021

Cell Reports Medicine

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Summary Although the BCG vaccine offers partial protection, tuberculosis remains a leading cause of infectious disease death, killing ∼1.5 million people annually. We developed mucosal vaccines expressing the autophagy-inducing peptide C5 and mycobacterial Ag85B-p25 epitope using replication-defective human adenovirus (HAdv 85C5 ) and bovine adenovirus (BAdv 85C5 ) vectors. BAdv 85C5 -infected dendritic cells (DCs) expressed a robust transcriptome of genes regulating antigen processing compared to HAdv 85C5 -infected DCs. BAdv 85C5 -infected DCs showed enhanced galectin-3/8 and autophagy-dependent in vitro Ag85B-p25 epitope presentation to CD4 T cells. BCG-vaccinated mice were intranasally boosted using HAdv 85C5 or BAdv 85C5 followed by infection using aerosolized Mycobacterium tuberculosis (Mtb). BAdv 85C5 protected mice against tuberculosis both as a booster after BCG vaccine (>1.4-log 10 reduction in Mtb lung burden) and as a single intranasal dose (>0.5-log 10 reduction). Protection was associated with robust CD4 and CD8 effector (T EM ), central memory (T CM ), and CD103 + /CD69 + lung-resident memory (T RM ) T cell expansion, revealing BAdv 85C5 as a promising mucosal vaccine for tuberculosis.

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“…Finally, current technology allows for cost‐effective production of high‐titred Ad vectors at a large scale. 12 , 78 Ad vectors exhibit transient transgene expression inside the host cells, thereby allowing an excellent environment for antigen presentation for developing humoral and CMI responses. 22 , 25 Ad vector technology for gene delivery has evolved over the years to address specific needs, including packaging capacity, reduced toxicity, the longevity of transgene expression and vector immunity.…”

Section: Ad Vector Typesmentioning

confidence: 99%

“…Even wild‐type Ads that cause asymptomatic or mild clinical symptoms in their natural hosts can be quickly rendered replication‐defective to further diminish unwanted side effects. Ad vectors infect various cells 12 and thereby can be used as systemic or mucosal vaccines. Importantly, they can quickly be produced and purified on a large scale at short notice offering billions of vaccine doses for clinical use.…”

Section: Introductionmentioning

confidence: 99%

Adenoviral vector‐based platforms for developing effective vaccines to combat respiratory viral infections

et al. 2021

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Since the development of the first vaccine against smallpox over two centuries ago, vaccination strategies have been at the forefront of significantly impacting the incidences of infectious diseases globally. However, the increase in the human population, deforestation and climate change, and the rise in worldwide travel have favored the emergence of new viruses with the potential to cause pandemics. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic is a cruel reminder of the impact of novel pathogens and the suboptimal capabilities of conventional vaccines. Therefore, there is an urgent need to develop new vaccine strategies that allow the production of billions of doses in a short duration and are broadly protective against emerging and re‐emerging infectious diseases. Extensive knowledge of the molecular biology and immunology of adenoviruses (Ad) has favored Ad vectors as platforms for vaccine design. The Ad‐based vaccine platform represents an attractive strategy as it induces robust humoral and cell‐mediated immune responses and can meet the global demand in a pandemic situation. This review describes the status of Ad vector‐based vaccines in preclinical and clinical studies for current and emerging respiratory viruses, particularly coronaviruses, influenza viruses and respiratory syncytial viruses.

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Current Use of Adenovirus Vectors and Their Production Methods

Cited by 24 publications

References 77 publications

Oncolytic adenovirus and gene therapy with EphA2-BiTE for the treatment of pediatric high-grade gliomas

Oncolytic adenovirus and gene therapy with EphA2-BiTE for the treatment of pediatric high-grade gliomas

A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice

Adenoviral vector‐based platforms for developing effective vaccines to combat respiratory viral infections

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