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The Regulatory Process and Gene Therapy
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
For adenovirus vectors, the analogous issue of replication-competent adenovirus (RCA) is of concern. Adenovirus infections of the respiratory tract are often mild, but could be significant adverse events in patients already compromised by lung diseases. Quantitative testing for presence of RCA is needed, and levels of RCA in patient doses are to be minimized.
Diagnostic Approach to Fulminant Hepatitis in the Critical Care Unit
Published in Cheston B. Cunha, Burke A. Cunha, Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Adenovirus is a ubiquitous double-stranded DNA virus that is an important cause of febrile illness in childhood. Rarely, adenovirus may disseminate and cause severe hepatic necrosis and fulminant hepatic failure, especially in immunocompromised hosts. Adenovirus hepatitis is a concern in pediatric liver transplant recipients, as it may be fatal. Transmission occurs through aerosolized droplets, fecal-oral exposure, or swimming pool water. The clinical features of ALF caused by adenovirus include high fevers, rapid rise in transaminases, hemodynamic instability, and a bleeding diathesis [39]. Detection of adenoviral infections in patients can be made through PCR, viral culture, or direct antigen assays [40]. Definitive diagnosis requires a liver biopsy. Immunohistochemically, adenovirus is characterized by intranuclear inclusion bodies in the biopsy material [41]. There is no specific therapy for adenovirus, and treatment includes fluids and supportive care.
Adenovirus
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Adenoviruses are endemic in the general population and are responsible for a spectrum of diseases ranging from mild upper respiratory tract infections to conjunctivitis, gastroenteritis, hepatitis, myocarditis, and life-threatening pulmonary disease. Such diseases can be more serious in pediatric and geriatric populations, and in individuals with suppressed immune systems. In particular, adenoviruses cause significant morbidity in AIDS, cancer, and organ transplant patients. Generally, however, adenoviruses cause minor, self-limiting illnesses in most patients. Adenovirus infections can be epidemic, endemic, or sporadic. Outbreaks involve day care facilities, schools, hospitals, children's camps, retirement homes, and military settings. Transmission may happen through direct contact with infected individuals, through the fecal-oral route or fomites. The virus is extremely resistant to different physical and chemical agents.
CXCL10-armed oncolytic adenovirus promotes tumor-infiltrating T-cell chemotaxis to enhance anti-PD-1 therapy
Published in OncoImmunology, 2022
Xiaofei Li, Mingjie Lu, Manman Yuan, Jing Ye, Wei Zhang, Lingyan Xu, Xiaohan Wu, Bingqing Hui, Yuchen Yang, Bin Wei, Ciliang Guo, Min Wei, Jie Dong, Xingxin Wu, Yanhong Gu
For the adenovirus replication assay, quantitative PCR was performed as previously reported.27 For tumor tissue mRNA analyses, total RNA was first isolated using TRIzol reagent (Takara Bio, Beijing, China), and cDNA was synthesized using PrimeScript RT Reagent Kits (Takara) according to the manufacturer’s recommendation. Quantitative RT–PCR was performed using SYBR Premix Ex Taq (Takara) and a CFX96 Real-time system (Bio–Rad Laboratories). The amplification program was as follows: one cycle of 95°C for 2 min, followed by 40 cycles of 95°C for 10s, 60°C for 30s, and 95°C for 10s.28 The primer sequences were as follows: viral skeleton protein gene (Hexon), forward 5’-ACCGTGAGGATACTGCGTAC-3’, reverse 5’-TTGCTCGTCTACTTCGTCTT-3’; mouse IFN-γ, forward 5’-ACAGCAAGGCGAAAAAGGATG-3’, reverse 5’-TGGTGGACCACTCGGATGA-3’; mouse Granzyme B, forward 5’-CCACTCTCGACCCTACATGG-3’, reverse 5’-GGCCCCCAAAGTGACATTTATT-3’ and mouse β-actin, forward 5’-GTGACGTTGACATCCGTAAAGA-3’, reverse 5’-GCCGGACTCATCGTACTCC-3’.
Uncovering key targets of success for immunotherapy in pancreatic cancer
Published in Expert Opinion on Therapeutic Targets, 2021
Andrea Pretta, Eleonora Lai, Mara Persano, Clelia Donisi, Giovanna Pinna, Erika Cimbro, Alissa Parrino, Dario Spanu, Stefano Mariani, Nicole Liscia, Marco Dubois, Marco Migliari, Valentino Impera, Giorgio Saba, Valeria Pusceddu, Marco Puzzoni, Pina Ziranu, Mario Scartozzi
Oncolytic viruses exploit the ability to integrate their genome with the host cell one, inducing viral replication and cell death, then allowing neoantigens to be released into the bloodstream and activate the immune system. Therefore, OVs have both oncolytic and immunostimulating properties. Hence, they offer the possibility of modulating immunosuppressive TME and inducing an inflammatory response, starting the recruitment of APC cells, CD8 + cytotoxic T cells and NK. To be effective, they have to replicate selectively in cancer cells and activate the immune system against elements of the cancer cell itself [80]. In the last twenty years, several OVs have been evaluated in preclinical and clinical trials. Most of these were engineered with gene-deletions or inclusions of genes encoding enzymes involved in chemotherapeutic drugs metabolism such as 5-FU. The viruses studied belonged to the families of adenoviridae, herpesviridae, reoviridae, and parvoviridae. Adenoviruses are the most widely studied both at the preclinical and clinical levels. One of the first to be evaluated was ONYX-015, which is selective for p53-deficient tumor cells, however, it showed poor clinical activity [81].
Merits of the ‘good’ viruses: the potential of virus-based therapeutics
Published in Expert Opinion on Biological Therapy, 2021
Qianyu Zhang, Wen Wu, Jinqiang Zhang, Xuefeng Xia
Adenoviruses are a class of DNA viruses with a double-stranded genome of around 36 kb. There are many serotypes of adenovirus, and the genome contains five early transcriptional units which become activated upon cell transfection (E1A, E1B, E2, E3, and E4), two delayed early transcriptional units (IX and IVa2), and one major late transcriptional unit (classified as L1, L2, L3, L4, and L5 genes) [60]. Unlike retroviral and lentiviral vectors, adenoviral vectors remain in an extrachromosomal state upon transduction. Although holding great potential in gene therapy due to their large packing capacity, their application has been limited due to their ability in eliciting high cellular immune response [61,62]. Besides that, adenovirus is a common infectious pathogen in humans, which might diminish its effectiveness as a therapeutic vehicle owing to the preexisting defensive mechanisms in vivo against adenovirus. In this regard, AAVs exhibited much improved properties since they are nonpathogenic parvovirus composed of a 4.7 kb single-stranded DNA genome within an icosahedral capsid [63]. Researches on AAVs have been gaining momentum in recent years. AAV vectors are well established in clinical trials for in vivo gene therapy. They possess broad tropism, low immunogenicity, and ease of production, and they can be further genetically engineered with improved properties. A recent review provided more details on the application of modified AAV vectors in gene therapy [64].