scholarly journals Strategies to Optimise Oncolytic Viral Therapies: The Role of Natural Killer Cells

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1450
Author(s):  
Elaine Y. L. Leung ◽  
Iain A. McNeish
Keyword(s):  
Clinical Trials ◽  
Nk Cells ◽  
Viral Infections ◽  
The United States ◽  
Oncolytic Viruses ◽  
Malignant Cells ◽  
Therapeutic Benefits ◽  
Viral Therapy ◽  
Potential Efficacy ◽  
Early Phase Clinical Trials

Oncolytic viruses (OVs) are an emerging class of anti-cancer agents that replicate selectively within malignant cells and generate potent immune responses. Their potential efficacy has been shown in clinical trials, with talimogene laherparepvec (T-VEC or IMLYGIC®) now approved both in the United States and Europe. In healthy individuals, NK cells provide effective surveillance against cancer and viral infections. In oncolytic viral therapy, NK cells may render OV ineffective by rapid elimination of the propagating virus but could also improve therapeutic efficacy by preferential killing of OV-infected malignant cells. Existing evidence suggests that the overall effect of NK cells against OV is context dependent. In the past decade, the understanding of cancer and OV biology has improved significantly, which helped refine this class of treatments in early-phase clinical trials. In this review, we summarised different strategies that have been evaluated to modulate NK activities for improving OV therapeutic benefits. Further development of OVs will require a systematic approach to overcome the challenges of the production and delivery of complex gene and cell-based therapies in clinical settings.

scholarly journals The Need for Antiviral Drugs for Pandemic Coronaviruses From a Global Health Perspective

2020 ◽  
Vol 7 ◽  
Author(s):  
Angela Holly Villamagna ◽  
Sara J. Gore ◽  
James S. Lewis ◽  
J. Stone Doggett
Keyword(s):  
Clinical Trials ◽  
Antiviral Therapy ◽  
Viral Infections ◽  
Disease Process ◽  
The United States ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Disease Stage ◽  
Symptom Duration ◽  
Oral Agents

Respiratory failure due to SARS-CoV-2 has caused widespread mortality, creating an urgent need for effective treatments and a long-term need for antivirals for future emergent coronaviruses. Pharmacotherapy for respiratory viruses has largely been unsuccessful with the exception of early treatment of influenza viruses, which shortens symptom duration and prevents infection in close contacts. Under the rapidly evolving circumstances of the COVID-19 pandemic, most clinical trials of experimental treatments in the United States have focused on later stages of the disease process. Worldwide, the clinical studies of the most impactful drugs, remdesivir and dexamethasone in ACTT-1, RECOVERY, and Solidarity, have studied hospitalized patients. Less than half of clinical trials in the U.S. have investigated oral agents, and the majority have taken place in hospitals at a disease stage where the viral load is already decreasing. The limited success of treatments for respiratory viruses and the viral dynamics of COVID-19 suggest that an antiviral therapy with the greatest impact against pandemic coronaviruses would be orally administered, well-tolerated, target a highly conserved viral protein or host-coronavirus interaction and could be used effectively throughout the world, including resource-poor settings. We examine the treatment of respiratory viral infections and current clinical trials for COVID-19 to provide a framework for effective antiviral therapy and prevention of future emergent coronaviruses and call attention to the need for continued preclinical drug discovery.

scholarly journals Oncolytic viruses for therapy of malignant glioma

2016 ◽  
Vol 62 (4) ◽  
pp. 376-390 ◽  
Author(s):  
A.O. Sosnovtceva ◽  
N.F. Grinenko ◽  
A.V. Lipatova ◽  
P.M. Chumakov ◽  
V.P. Chekhonin
Keyword(s):  
Clinical Trials ◽  
Tumor Cells ◽  
Disease Recurrence ◽  
Oncolytic Viruses ◽  
High Rate ◽  
Glial Tumor ◽  
Viral Therapy ◽  
The Brain ◽  
Virus Strains ◽  
Single Tumor

Effective treatment of malignant brain tumors is still an open problem. Location of tumor in vital areas of the brain significantly limits capasities of surgical treatment. The presence of tumor stem cells resistant to radiation and anticancer drugs in brain tumor complicates use of chemoradiotherapy and causes a high rate of disease recurrence. A technological improvement in bioselection and production of recombinant resulted in creation of viruses with potent oncolytic properties against glial tumors. Recent studies, including clinical trials, showed, that majority of oncolytic viruses are safe. Despite the impressive results of the viral therapy in some patients, the treatment of other patients is not effective; therefore, further improvement of the methods of oncolytic virotherapy is necessary. High genetic heterogeneity of glial tumor cells even within a single tumor determines differences in individual sensitivity of tumor cells to oncolytic viruses. This review analyses the most successful oncolytic virus strains, including those which had reached clinical trials, and discusses the prospects for new approaches to virotherapy of gliomas.

scholarly journals Oncolytic Virotherapy for Cancer: Clinical Experience

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 419
Author(s):  
Shyambabu Chaurasiya ◽  
Yuman Fong ◽  
Susanne G. Warner
Keyword(s):  
Clinical Trials ◽  
Rna Viruses ◽  
Rna Virus ◽  
Genetically Engineered ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Dna Viruses ◽  
New Class ◽  
Therapeutic Benefits ◽  
Experimental Stage

Oncolytic viruses are a new class of therapeutics which are largely in the experimental stage, with just one virus approved by the FDA thus far. While the concept of oncolytic virotherapy is not new, advancements in the fields of molecular biology and virology have renewed the interest in using viruses as oncolytic agents. Backed by robust preclinical data, many oncolytic viruses have entered clinical trials. Oncolytic viruses that have completed some levels of clinical trials or are currently undergoing clinical trials are mostly genetically engineered viruses, with the exception of some RNA viruses. Reolysin, an unmodified RNA virus is clinically the most advanced oncolytic RNA virus that has completed different phases of clinical trials. Other oncolytic viruses that have been studied in clinical trials are mostly DNA viruses that belong to one of the three families: herpesviridae, poxviridae or adenoviridae. In this review work we discuss recent clinical studies with oncolytic viruses, especially herpesvirus, poxvirus, adenovirus and reovirus. In summary, the oncolytic viruses tested so far are well tolerated, even in immune-suppressed patients. For most oncolytic viruses, mild and acceptable toxicities are seen at the currently defined highest feasible doses. However, anti-tumor efficacies of oncolytic viruses have been modest, especially when used as monotherapy. Therefore, the potency of oncolytic viruses needs to be enhanced for more oncolytic viruses to hit the clinic. Aiming to achieve higher therapeutic benefits, oncolytic viruses are currently being studied in combination with other therapies. Here we discuss the currently available clinical data on oncolytic viruses, either as monotherapy or in combination with other treatments.

scholarly journals Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection

2017 ◽  
Vol 24 (12) ◽  
Author(s):  
Mark R. Schleiss ◽  
Sallie R. Permar ◽  
Stanley A. Plotkin
Keyword(s):  
Public Health ◽  
Clinical Trials ◽  
Health Impact ◽  
The United States ◽  
Vaccine Trials ◽  
Potential Efficacy ◽  
The Status ◽  
The Face ◽  
Cmv Disease ◽  
Congenital Cmv

ABSTRACT A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice.

scholarly journals Oncolytic Virotherapy for Multiple Myeloma: Past, Present, and Future

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Chandini M. Thirukkumaran ◽  
Don G. Morris
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Anticancer Agents ◽  
Measles Virus ◽  
Clinical Investigation ◽  
Cancer Therapeutics ◽  
Oncolytic Viruses ◽  
Treatment Modalities ◽  
Dna And Rna ◽  
Viral Therapy

Multiple myeloma (MM) is a B-cell malignancy that is currently felt to be incurable. Despite recently approved novel targeted treatments such as lenalidomide and bortezomib, most MM patients' relapse is emphasizing the need for effective and well-tolerated therapies for this deadly disease. The use of oncolytic viruses has garnered significant interest as cancer therapeutics in recent years, and are currently under intense clinical investigation. Both naturally occurring and engineered DNA and RNA viruses have been investigated preclinically as treatment modalities for several solid and hematological malignancies. Presently, only a genetically modified measles virus is in human clinical trials for MM. The information obtained from this and other future clinical trials will guide clinical application of oncolytic viruses as anticancer agents for MM. This paper provides a timely overview of the history of oncolytic viruses for the treatment of MM and future strategies for the optimization of viral therapy for this disease.

scholarly journals Systemic Delivery of Oncolytic Viruses: Hopes and Hurdles

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Mark S. Ferguson ◽  
Nicholas R. Lemoine ◽  
Yaohe Wang
Keyword(s):  
Clinical Trials ◽  
Primary Tumour ◽  
Oncolytic Viruses ◽  
Viral Escape ◽  
Systemic Delivery ◽  
Stage Of Development ◽  
Viral Therapy ◽  
Rapid Clearance ◽  
Novel Therapeutic Strategies ◽  
Vascular Compartment

Despite recent advances in both surgery and chemoradiotherapy, mortality rates for advanced cancer remain high. There is a pressing need for novel therapeutic strategies; one option is systemic oncolytic viral therapy. Intravenous administration affords the opportunity to treat both the primary tumour and any metastatic deposits simultaneously. Data from clinical trials have shown that oncolytic viruses can be systemically delivered safely with limited toxicity but the results are equivocal in terms of efficacy, particularly when delivered with adjuvant chemotherapy. A key reason for this is the rapid clearance of the viruses from the circulation before they reach their targets. This phenomenon is mainly mediated through neutralising antibodies, complement activation, antiviral cytokines, and tissue-resident macrophages, as well as nonspecific uptake by other tissues such as the lung, liver and spleen, and suboptimal viral escape from the vascular compartment. A range of methods have been reported in the literature, which are designed to overcome these hurdles in preclinical models. In this paper, the potential advantages of, and obstacles to, successful systemic delivery of oncolytic viruses are discussed. The next stage of development will be the commencement of clinical trials combining these novel approaches for overcoming the barriers with systemically delivered oncolytic viruses.

Developing a Clinical Trials Infrastructure in the United States

2012 ◽  
Vol 2 (5) ◽  
Author(s):  
Paul Eisenberg ◽  
◽  
Petra Kaufmann ◽  
Ellen Sigal ◽  
Janet Woodcock ◽  
...  
Keyword(s):  
United States ◽  
Clinical Trials ◽  
The United States

Antibody Therapy for the Control of Viral Diseases: An Update

2019 ◽  
Vol 20 (13) ◽  
pp. 1108-1121 ◽  
Author(s):  
Miriam Dibo ◽  
Eduardo C. Battocchio ◽  
Lucas M. dos Santos Souza ◽  
Matheus D. Veloso da Silva ◽  
Bruna K. Banin-Hirata ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Viral Antigen ◽  
Viral Infections ◽  
Antibody Therapy ◽  
Therapeutic Strategies ◽  
Viral Diseases ◽  
Specific Antibodies ◽  
The Status ◽  
Epidemiological Impact

The epidemiological impact of viral diseases, combined with the emergence and reemergence of some viruses, and the difficulties in identifying effective therapies, have encouraged several studies to develop new therapeutic strategies for viral infections. In this context, the use of immunotherapy for the treatment of viral diseases is increasing. One of the strategies of immunotherapy is the use of antibodies, particularly the monoclonal antibodies (mAbs) and multi-specific antibodies, which bind directly to the viral antigen and bring about activation of the immune system. With current advancements in science and technology, several such antibodies are being tested, and some are already approved and are undergoing clinical trials. The present work aims to review the status of mAb development for the treatment of viral diseases.

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