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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 -
The Lancet. Infectious Diseases Jun 2020Measles eradication is biologically and technically feasible, but suboptimal immunisation programme performance, insufficient political commitment, overcautious global... (Review)
Review
Measles eradication is biologically and technically feasible, but suboptimal immunisation programme performance, insufficient political commitment, overcautious global agencies, and inadequate prioritisation by important donors are hindering progress towards this noble public health goal. These constraints have given rise to a global resurgence in measles cases and preventable deaths, with re-established transmission in countries that have previously eliminated endemic virus transmission. The ethical, economic, and epidemiological reasons for accelerating progress towards eradication are irrefutable. Measles virus also serves as the most sensitive test of universal health coverage. Where health systems are not reaching all susceptible children and communities, the presence of measles cases will expose and proclaim this failure. The global health community should urgently intensify efforts to eradicate measles.
Topics: Disease Eradication; Humans; Measles; Measles Vaccine
PubMed: 32197095
DOI: 10.1016/S1473-3099(20)30052-9 -
Workplace Health & Safety Feb 2020Outbreaks of measles increased in the United States in 2019. Occupational health nurses need to be aware of this highly infectious disease, disseminate accurate...
Outbreaks of measles increased in the United States in 2019. Occupational health nurses need to be aware of this highly infectious disease, disseminate accurate information, and emphasize the benefits of immunization to workers.
Topics: Disease Outbreaks; Humans; Immunization; Measles; Measles virus; Measles-Mumps-Rubella Vaccine; Occupational Health Nursing; United States
PubMed: 31910782
DOI: 10.1177/2165079919890354 -
Viruses Sep 2020Viruses have been repurposed into tools for gene delivery by transforming them into viral vectors. The most frequently used vectors are lentiviral vectors (LVs), derived... (Review)
Review
Viruses have been repurposed into tools for gene delivery by transforming them into viral vectors. The most frequently used vectors are lentiviral vectors (LVs), derived from the human immune deficiency virus allowing efficient gene transfer in mammalian cells. They represent one of the safest and most efficient treatments for monogenic diseases affecting the hematopoietic system. LVs are modified with different viral envelopes (pseudotyping) to alter and improve their tropism for different primary cell types. The vesicular stomatitis virus glycoprotein (VSV-G) is commonly used for pseudotyping as it enhances gene transfer into multiple hematopoietic cell types. However, VSV-G pseudotyped LVs are not able to confer efficient transduction in quiescent blood cells, such as hematopoietic stem cells (HSC), B and T cells. To solve this problem, VSV-G can be exchanged for other heterologous viral envelopes glycoproteins, such as those from the Measles virus, Baboon endogenous retrovirus, Cocal virus, Nipah virus or Sendai virus. Here, we provide an overview of how these LV pseudotypes improved transduction efficiency of HSC, B, T and natural killer (NK) cells, underlined by multiple in vitro and in vivo studies demonstrating how pseudotyped LVs deliver therapeutic genes or gene editing tools to treat different genetic diseases and efficiently generate CAR T cells for cancer treatment.
Topics: Animals; CRISPR-Cas Systems; Gene Editing; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Hematopoietic Stem Cells; Humans; Killer Cells, Natural; Lentivirus; Measles virus; Membrane Glycoproteins; Nipah Virus; Research; T-Lymphocytes; Vesicular stomatitis Indiana virus; Viral Envelope Proteins
PubMed: 32933033
DOI: 10.3390/v12091016 -
Nature Reviews. Microbiology Nov 2021
PubMed: 34408295
DOI: 10.1038/s41579-021-00629-1 -
Frontiers in Microbiology 2019Measles virus is a negative strand virus and the genomic and antigenomic RNA binds to the nucleoprotein (N), assembling into a helical nucleocapsid. The polymerase... (Review)
Review
Measles virus is a negative strand virus and the genomic and antigenomic RNA binds to the nucleoprotein (N), assembling into a helical nucleocapsid. The polymerase complex comprises two proteins, the Large protein (L), that both polymerizes RNA and caps the mRNA, and the phosphoprotein (P) that co-localizes with L on the nucleocapsid. This review presents recent results about N and P, in particular concerning their intrinsically disordered domains. N is a protein of 525 residues with a 120 amino acid disordered C-terminal domain, N. The first 50 residues of N extricate the disordered chain from the nucleocapsid, thereby loosening the otherwise rigid structure, and the C-terminus contains a linear motif that binds P. Recent results show how the 5' end of the viral RNA binds to N within the nucleocapsid and also show that the bases at the 3' end of the RNA are rather accessible to the viral polymerase. P is a tetramer and most of the protein is disordered; comprising 507 residues of which around 380 are disordered. The first 37 residues of P bind N, chaperoning against non-specific interaction with cellular RNA, while a second interaction site, around residue 200 also binds N. In addition, there is another interaction between C-terminal domain of P (XD) and N. These results allow us to propose a new model of how the polymerase binds to the nucleocapsid and suggests a mechanism for initiation of transcription.
PubMed: 31496998
DOI: 10.3389/fmicb.2019.01832 -
Current Opinion in Virology Apr 2020Measles caused an estimated minimum of one million fatalities annually before vaccination. Outstanding progress towards controlling the virus has been made since the... (Review)
Review
Measles caused an estimated minimum of one million fatalities annually before vaccination. Outstanding progress towards controlling the virus has been made since the measles vaccine was introduced, but reduction of measles case-fatalities has stalled at around 100,000 annually for the last decade and a 2019 resurgence in several geographical regions threatens some of these past accomplishments. Whereas measles eradication through vaccination is feasible, a potentially open-ended endgame of elimination may loom. Other than doubling-down on existing approaches, is it worthwhile to augment vaccination efforts with antiviral therapeutics to solve the conundrum? This question is hypothetical at present, since no drugs have yet been approved specifically for the treatment of measles, or infection by any other pathogen of the paramyxovirus family. This article will consider obstacles that have hampered anti-measles and anti-paramyxovirus drug development, discuss MeV-specific challenges of clinical testing, and define drug properties suitable to address some of these problems.
Topics: Animals; Antiviral Agents; Drug Development; Global Health; Humans; Measles; Measles Vaccine; Measles virus
PubMed: 32247280
DOI: 10.1016/j.coviro.2020.02.007 -
Seminars in Pediatric Neurology Oct 2023Sequelae Renee Buchanan, Daniel J. Bonthius Seminars in Pediatric Neurology Volume 19, Issue 3, September 2012, Pages 107-114 Worldwide, measles remains one of the most...
Sequelae Renee Buchanan, Daniel J. Bonthius Seminars in Pediatric Neurology Volume 19, Issue 3, September 2012, Pages 107-114 Worldwide, measles remains one of the most deadly vaccine-preventable diseases. In the United States, enrollment in the public schools requires that each child receives 2 doses of measles-containing vaccine before entry, essentially eliminating this once endemic disease. Recent outbreaks of measles in the United States have been associated with importation of measles virus from other countries and subsequent transmission to intentionally undervaccinated children. The central nervous system complications of measles can occur within days or years of acute infection and are often severe. These include primary measles encephalitis, acute postinfectious measles encephalomyelitis, measles inclusion body encephalitis, and subacute sclerosing panencephalitis. These measles associated central nervous system diseases differ in their pathogenesis and pathologic effects. However, all involve complex brain-virus-immune system interactions, and all can lead to severe and permanent brain injury. Despite better understanding of the clinical presentations and pathogenesis of these illnesses, effective treatments remain elusive.
Topics: Child; Humans; Measles virus; Central Nervous System; Measles; Subacute Sclerosing Panencephalitis; Brain; Encephalomyelitis, Acute Disseminated
PubMed: 37919033
DOI: 10.1016/j.spen.2023.101078 -
Cancers Feb 2021Measles virus (MeV) preferentially replicates in malignant cells, leading to tumor lysis and priming of antitumor immunity. Live attenuated MeV vaccine strains are... (Review)
Review
Measles virus (MeV) preferentially replicates in malignant cells, leading to tumor lysis and priming of antitumor immunity. Live attenuated MeV vaccine strains are therefore under investigation as cancer therapeutics. The versatile MeV reverse genetics systems allows for engineering of advanced targeted, armed, and shielded oncolytic viral vectors. Therapeutic efficacy can further be enhanced by combination treatments. An emerging focus in this regard is combination immunotherapy, especially with immune checkpoint blockade. Despite challenges arising from antiviral immunity, availability of preclinical models, and GMP production, early clinical trials have demonstrated safety of oncolytic MeV and yielded promising efficacy data. Future clinical trials with engineered viruses, rational combination regimens, and comprehensive translational research programs will realize the potential of oncolytic immunotherapy.
PubMed: 33535479
DOI: 10.3390/cancers13030544 -
Viruses Nov 2019Measles remains a major cause of morbidity and mortality worldwide among vaccine preventable diseases. Recent decline in vaccination coverage resulted in re-emergence of... (Review)
Review
Measles remains a major cause of morbidity and mortality worldwide among vaccine preventable diseases. Recent decline in vaccination coverage resulted in re-emergence of measles outbreaks. Measles virus (MeV) infection causes an acute systemic disease, associated in certain cases with central nervous system (CNS) infection leading to lethal neurological disease. Early following MeV infection some patients develop acute post-infectious measles encephalitis (APME), which is not associated with direct infection of the brain. MeV can also infect the CNS and cause sub-acute sclerosing panencephalitis (SSPE) in immunocompetent people or measles inclusion-body encephalitis (MIBE) in immunocompromised patients. To date, cellular and molecular mechanisms governing CNS invasion are still poorly understood. Moreover, the known MeV entry receptors are not expressed in the CNS and how MeV enters and spreads in the brain is not fully understood. Different antiviral treatments have been tested and validated in vitro, ex vivo and in vivo mainly in small animal models. Most treatments have high efficacy at preventing infection but their effectiveness after CNS manifestations remains to be evaluated. This review describes MeV neural infection and current most advanced therapeutic approaches potentially applicable to treat MeV CNS infection.
Topics: Animals; Antiviral Agents; Central Nervous System; Disease Models, Animal; Encephalitis, Viral; Humans; Measles; Measles virus; Viral Proteins; Viral Tropism
PubMed: 31684034
DOI: 10.3390/v11111017