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Expert Opinion on Biological Therapy 2023Many pediatric patients with malignant tumors continue to suffer poor outcomes. The current standard of care includes maximum safe surgical resection followed by... (Review)
Review
INTRODUCTION
Many pediatric patients with malignant tumors continue to suffer poor outcomes. The current standard of care includes maximum safe surgical resection followed by chemotherapy and radiation which may be associated with considerable long-term morbidity. The emergence of oncolytic virotherapy (OVT) may provide an alternative or adjuvant treatment for pediatric oncology patients.
AREAS COVERED
We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). For each virus, we discuss the mechanism of tumor-specific replication and cytotoxicity as well as key findings of preclinical and clinical studies.
EXPERT OPINION
Substantial progress has been made in the past 10 years regarding the clinical use of OVT. From our review, OVT has favorable safety profiles compared to chemotherapy and radiation treatment. However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future.
Topics: Humans; Child; Oncolytic Virotherapy; Oncolytic Viruses; Neoplasms; Simplexvirus; Vaccinia virus; Genetic Therapy
PubMed: 37749907
DOI: 10.1080/14712598.2023.2245326 -
Current Opinion in Ophthalmology Nov 2023This review broadly describes recent neuro-ophthalmic manifestations of varicella-zoster virus (VZV) reported in literature. (Review)
Review
PURPOSE OF REVIEW
This review broadly describes recent neuro-ophthalmic manifestations of varicella-zoster virus (VZV) reported in literature.
RECENT FINDINGS
Despite varicella vaccination, the incidence of herpes zoster continues to rise, potentially leading to devastating consequences when ocular complications occur.A small but growing literature documents cases of retinal disease because of varicella reactivation after SARS-CoV-2 vaccination, ischemic optic neuropathy occurring during herpes zoster ophthalmicus, VZV-induced orbital apex syndrome, and immune-mediated ocular complications in patients with prior neuro-ophthalmic manifestations of VZV.
SUMMARY
It is important for clinicians to keep abreast of the diverse neuro-ophthalmic manifestations of VZV as early diagnosis and treatment often lead to better visual outcomes.
Topics: Humans; Herpesvirus 3, Human; Chickenpox; COVID-19 Vaccines; COVID-19; SARS-CoV-2
PubMed: 37603549
DOI: 10.1097/ICU.0000000000000996 -
Neuroimaging Clinics of North America Feb 2024Stroke is a complication of many central nervous system (CNS) infections, but only a few present with stroke without other symptoms or signs of CNS infection. Chief... (Review)
Review
Stroke is a complication of many central nervous system (CNS) infections, but only a few present with stroke without other symptoms or signs of CNS infection. Chief among these are varicella zoster virus (VZV) and syphilis. Delayed cerebral vasculopathy after successful treatment of bacterial meningitis, most commonly pneumococcal, is an emerging entity with uncertain pathogenesis.
Topics: Humans; Herpes Zoster; Herpesvirus 3, Human; Stroke
PubMed: 37951699
DOI: 10.1016/j.nic.2023.06.001 -
Current Opinion in Virology Oct 2023Microtubule transport and nuclear import are functionally connected, and the nuclear pore complex (NPC) can interact with microtubule motors. For several... (Review)
Review
Microtubule transport and nuclear import are functionally connected, and the nuclear pore complex (NPC) can interact with microtubule motors. For several alphaherpesvirus proteins, nuclear localization signals (NLSs) and their interactions with specific importin-α proteins have been characterized. Here, we review recent insights on the roles of microtubule motors, capsid-associated NLSs, and importin-α proteins for capsid transport, capsid docking to NPCs, and genome release into the nucleoplasm, as well as the role of importins for nuclear viral transcription, replication, capsid assembly, genome packaging, and nuclear capsid egress. Moreover, importin-α proteins exert antiviral effects by promoting the nuclear import of transcription factors inducing the expression of interferons (IFN), cytokines, and IFN-stimulated genes, and the IFN-inducible MxB restricts capsid docking to NPCs.
Topics: Humans; Karyopherins; alpha Karyopherins; Nuclear Pore; Herpes Simplex; Alphaherpesvirinae; Capsid Proteins
PubMed: 37672874
DOI: 10.1016/j.coviro.2023.101361 -
Immunity, Inflammation and Disease Oct 2023This study investigated the proteomic characteristics of cerebrospinal fluid (CSF) in patients with varicella zoster virus (VZV) meningitis to understanding the... (Review)
Review
OBJECTIVE
This study investigated the proteomic characteristics of cerebrospinal fluid (CSF) in patients with varicella zoster virus (VZV) meningitis to understanding the pathogenesis of central nervous system (CNS) infection by reactivated VZV.
METHOD
We used data-independent acquisition model to analyze the CSF proteomic differences of 28 patients with VZV meningitis and 11 herpes zoster (HZ) patients. According to the clinical manifestations at discharge, 28 VZV meningitis patients were divided into favorable outcome group and unfavorable outcome (UO) group and their differences in CSF proteome were also analyzed.
RESULTS
Compared with the HZ group, the proteins (CXCL10, ELANE, IL-1RN, MPO, PRTN3, etc.) related to inflammation and immune cell activation were significantly upregulated in the VZV meningitis group (p < .01). The protein related to the nerve function and energy metabolism (CKMT1B, SLITRK3, Synaptotagmin-3, KIF5B, etc.) were significantly downregulated (p < .05). The levels of a pro-inflammatory factor, IL-18, in CSF were significantly higher in patients in the UO group as compared to patients with favorable prognosis (p < .05).
CONCLUSION
Inflammatory immune response is an important pathophysiological mechanism of CNS infection by VZV, and the CSF IL-18 levels might be a potential prognostic indicator of the outcomes of VZV meningitis.
Topics: Humans; Herpesvirus 3, Human; Interleukin-18; Proteomics; Herpes Zoster; Meningitis; Proteins
PubMed: 37904697
DOI: 10.1002/iid3.1038 -
Human Vaccines & Immunotherapeutics Dec 2023The recombinant zoster vaccine (RZV) was licensed in the US for prevention of herpes zoster (HZ) in 2017. We conducted a literature search (January 1, 2017-August 1,... (Review)
Review
The recombinant zoster vaccine (RZV) was licensed in the US for prevention of herpes zoster (HZ) in 2017. We conducted a literature search (January 1, 2017-August 1, 2023) using PubMed, Embase, and Scopus to consolidate the real-world evidence related to RZV. Overall, RZV effectiveness against HZ was high across the studied populations in real-world settings, including adults aged ≥ 50 years and patients aged ≥ 18 years with immunodeficiency or immunosuppression. Effectiveness was higher with two doses versus one dose, especially in elderly people and immunocompromised individuals. The safety profile of RZV was broadly consistent with that established in clinical trials. RZV does not appear to increase the risk of disease flares in patients with immune-mediated diseases. Approximately two-thirds of individuals received a second RZV dose within 2-6 months after the first dose. Collectively, RZV effectiveness against HZ was high, and these real-world studies reaffirm its favorable benefit-risk profile.
Topics: Aged; Humans; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Immunocompromised Host; Vaccines, Synthetic; Adolescent; Adult; Middle Aged
PubMed: 37967254
DOI: 10.1080/21645515.2023.2263979 -
Graefe's Archive For Clinical and... Aug 2023While typically affecting older adults and immunocompromised individuals, herpes zoster ophthalmicus (HZO) has been reported with varying manifestations and... (Review)
Review
PURPOSE
While typically affecting older adults and immunocompromised individuals, herpes zoster ophthalmicus (HZO) has been reported with varying manifestations and complications in children. In this review, we evaluate reported cases of pediatric HZO in the literature and discuss the epidemiology, risk factors, clinical presentation, treatment and outcomes.
METHODS
A literature search on PubMed, Scopus, and Web of Science databases was performed using the terms "pediatric herpes zoster ophthalmicus" and "herpes zoster ophthalmicus children." Publications that were not specific to HZO or pediatric populations were excluded, as were publications that were not available to review or not published in the English language.
RESULTS
Fifty-seven reports describing 130 cases of HZO or HZO-related complications were reviewed. Major risk factors for pediatric HZO included intrauterine exposure to varicella or primary varicella infection at a young age; HZO also occurred in patients who had received varicella vaccination. Both healthy and immunocompromised children were affected, with the majority of affected children being immunocompetent. The diagnosis of HZO is primarily clinical. Children appear to have good vision recovery and resolution of symptoms if they are treated promptly and if they adhere to treatment regimens, except for irreversible vision loss related to uncommon complications such as optic neuritis.
CONCLUSION
HZO occurs in both healthy and immunocompromised children. Recognizing this treatable condition is essential for reducing ocular and systemic morbidity. Long-term follow-up and assessments of the impact on health in adulthood are lacking. More systematic study is needed to determine the incidence of HZO in children and appropriate diagnostic and treatment protocols for the care of pediatric patients with HZO.
Topics: Humans; Child; Aged; Herpes Zoster Ophthalmicus; Chickenpox; Herpesvirus 3, Human; Incidence; Morbidity
PubMed: 36949170
DOI: 10.1007/s00417-023-06033-0 -
Nature Communications Jan 2024Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are...
Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are associated with cancer progression, yet their formation mechanism and role in oncolytic virotherapy remain elusive. In this study, we demonstrate that, in glioma, upregulation of IGF2BP3 enhances the expression of E3 ubiquitin protein ligase MIB1, promoting FTO degradation via the ubiquitin-proteasome pathway. This results in increased m6A-mediated CSF3 release and NET formation. Oncolytic herpes simplex virus (oHSV) stimulates IGF2BP3-induced NET formation in malignant glioma. In glioma models in female mice, a BET inhibitor enhances the oncolytic activity of oHSV by impeding IGF2BP3-induced NETosis, reinforcing virus replication through BRD4 recruitment with the CDK9/RPB-1 complex to HSV gene promoters. Our findings unveil the regulation of m6A-mediated NET formation, highlight oncolytic virus-induced NETosis as a critical checkpoint hindering oncolytic potential, and propose targeting NETosis as a strategy to overcome resistance in oncolytic virotherapy.
Topics: Female; Mice; Animals; Oncolytic Virotherapy; Drug Resistance, Neoplasm; Nuclear Proteins; Transcription Factors; Glioma; Simplexvirus; Oncolytic Viruses
PubMed: 38167409
DOI: 10.1038/s41467-023-44576-2 -
Frontiers in Immunology 2023Recurrent glioma treatment is challenging due to molecular heterogeneity and treatment resistance commonly observed in these tumors. Researchers are actively pursuing... (Review)
Review
Recurrent glioma treatment is challenging due to molecular heterogeneity and treatment resistance commonly observed in these tumors. Researchers are actively pursuing new therapeutic strategies. Oncolytic viruses have emerged as a promising option. Oncolytic viruses selectively replicate within tumor cells, destroying them and stimulating the immune system for an enhanced anticancer response. Among Oncolytic viruses investigated for recurrent gliomas, oncolytic herpes simplex virus and oncolytic adenovirus show notable potential. Genetic modifications play a crucial role in optimizing their therapeutic efficacy. Different generations of replicative conditioned oncolytic human adenovirus and oncolytic HSV have been developed, incorporating specific modifications to enhance tumor selectivity, replication efficiency, and immune activation. This review article summarizes these genetic modifications, offering insights into the underlying mechanisms of Oncolytic viruses' therapy. It also aims to identify strategies for further enhancing the therapeutic benefits of Oncolytic viruses. However, it is important to acknowledge that additional research and clinical trials are necessary to establish the safety, efficacy, and optimal utilization of Oncolytic viruses in treating recurrent glioblastoma.
Topics: Humans; Simplexvirus; Adenoviridae; Neoplasm Recurrence, Local; Glioma; Oncolytic Viruses; Adenoviridae Infections
PubMed: 38022620
DOI: 10.3389/fimmu.2023.1285113 -
Viruses Nov 2023Oncolytic viruses (OVs) have emerged as one of the most promising cancer immunotherapy agents that selectively target and kill cancer cells while sparing normal cells.... (Review)
Review
Oncolytic viruses (OVs) have emerged as one of the most promising cancer immunotherapy agents that selectively target and kill cancer cells while sparing normal cells. OVs are from diverse families of viruses and can possess either a DNA or an RNA genome. These viruses also have either a natural or engineered tropism for cancer cells. Oncolytic DNA viruses have the additional advantage of a stable genome and multiple-transgene insertion capability without compromising infection or replication. Herpes simplex virus 1 (HSV-1), a member of the oncolytic DNA viruses, has been approved for the treatment of cancers. This success with HSV-1 was achievable by introducing multiple genetic modifications within the virus to enhance cancer selectivity and reduce the toxicity to healthy cells. Here, we review the natural characteristics of and genetically engineered changes in selected DNA viruses that enhance the tumor tropism of these oncolytic viruses.
Topics: Humans; Oncolytic Virotherapy; Neoplasms; Herpesvirus 1, Human; Oncolytic Viruses; Tropism; DNA Viruses
PubMed: 38005938
DOI: 10.3390/v15112262