Oncolytic virotherapy as promising immunotherapy against cancer: mechanisms of resistance to oncolytic viruses

2021 ◽  
Author(s):  
Nasser Hashemi Goradel ◽  
Arezoo Alizadeh ◽  
Shahnaz Hosseinzadeh ◽  
Mitra Taghipour ◽  
Zeinab Ghesmati ◽  
...  
Keyword(s):  
Immune Responses ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Early 20Th Century ◽  
Mechanisms Of Resistance ◽  
Talimogene Laherparepvec ◽  
Aberrant Expression ◽  
Expression Of Genes ◽  
History Of ◽  
Interferon Responses

Oncolytic virotherapy has currently emerged as a powerful therapeutic approach in cancer treatment. Although the history of using viruses goes back to the early 20th century, the approval of talimogene laherparepvec (T-VEC) in 2015 increased interest in oncolytic viruses (OVs). OVs are multifaceted biotherapeutic agents because they replicate in and kill tumor cells and augment immune responses by releasing immunostimulatory molecules from lysed cells. Despite promising results, some limitations hinder the efficacy of oncolytic virotherapy. The delivery challenges and the upregulation of checkpoints following oncolytic virotherapy also mediate resistance to OVs by diminishing immune responses. Furthermore, the localization of receptors of viruses in the tight junctions, interferon responses, and the aberrant expression of genes involved in the cell cycle of the virus, including their infection and replication, reduce the efficacy of OVs. In this review, we present different mechanisms of resistance to OVs and strategies to overcome them.

scholarly journals In Situ Cancer Vaccination and Immunovirotherapy Using Oncolytic HSV

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1740
Author(s):  
Nusrat Jahan ◽  
Shanawaz M. Ghouse ◽  
Robert L. Martuza ◽  
Samuel D. Rabkin
Keyword(s):  
Immune Responses ◽  
Advanced Melanoma ◽  
Oncolytic Viruses ◽  
Abscopal Effect ◽  
Immunocompetent Mouse ◽  
Talimogene Laherparepvec ◽  
Normal Cells ◽  
Cancer Vaccination ◽  
Simplex Virus

Herpes simplex virus (HSV) can be genetically altered to acquire oncolytic properties so that oncolytic HSV (oHSV) preferentially replicates in and kills cancer cells, while sparing normal cells, and inducing anti-tumor immune responses. Over the last three decades, a better understanding of HSV genes and functions, and improved genetic-engineering techniques led to the development of oHSV as a novel immunovirotherapy. The concept of in situ cancer vaccination (ISCV) was first introduced when oHSV was found to induce a specific systemic anti-tumor immune response with an abscopal effect on non-injected tumors, in the process of directly killing tumor cells. Thus, the use of oHSV for tumor vaccination in situ is antigen-agnostic. The research and development of oHSVs have moved rapidly, with the field of oncolytic viruses invigorated by the FDA/EMA approval of oHSV talimogene laherparepvec in 2015 for the treatment of advanced melanoma. Immunovirotherapy can be enhanced by arming oHSV with immunomodulatory transgenes and/or using them in combination with other chemotherapeutic and immunotherapeutic agents. This review offers an overview of the development of oHSV as an agent for ISCV against solid tumors, describing the multitude of different oHSVs and their efficacy in immunocompetent mouse models and in clinical trials.

scholarly journals Designer nanocarriers for navigating the systemic delivery of oncolytic viruses

Nanomedicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 93-110 ◽  
Author(s):  
Faith Howard ◽  
Munitta Muthana
Keyword(s):  
Optimal Design ◽  
Immune Responses ◽  
Systemic Administration ◽  
Oncolytic Viruses ◽  
Cellular Interaction ◽  
Oncolytic Virotherapy ◽  
Specific Cell ◽  
Systemic Delivery ◽  
Cell Binding ◽  
Carrier Systems

Nanotechnology is paving the way for new carrier systems designed to overcome the greatest challenges of oncolytic virotherapy; systemic administration and subsequent implications of immune responses and specific cell binding and entry. Systemic administration of oncolytic agents is vital for disseminated neoplasms, however transition of nanoparticles (NP) to virotherapy has yielded modest results. Their success relies on how they navigate the merry-go-round of often-contradictory phases of NP delivery: circulatory longevity, tissue permeation and cellular interaction, with many studies postulating design features optimal for each phase. This review discusses the optimal design of NPs for the transport of oncolytic viruses within these phases, to determine whether improved virotherapeutic efficacy lies in the pharmacokinetic/pharmacodynamics characteristics of the NP–oncolytic viruses complexes rather than manipulation of the virus and targeting ligands.

scholarly journals Oncolytic Viruses: Newest Frontier for Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5452
Author(s):  
Masmudur M. Rahman ◽  
Grant McFadden
Keyword(s):  
Clinical Trials ◽  
Immune Responses ◽  
Cancer Patient ◽  
Cancer Cells ◽  
Treatment Modality ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Therapeutic Approaches ◽  
Cancer Treatments ◽  
The Past

Cancer remains a leading cause of death worldwide. Despite many signs of progress, currently available cancer treatments often do not provide desired outcomes for too many cancers. Therefore, newer and more effective therapeutic approaches are needed. Oncolytic viruses (OVs) have emerged as a novel cancer treatment modality, which selectively targets and kills cancer cells while sparing normal ones. In the past several decades, many different OV candidates have been developed and tested in both laboratory settings as well as in cancer patient clinical trials. Many approaches have been taken to overcome the limitations of OVs, including engineering OVs to selectively activate anti-tumor immune responses. However, newer approaches like the combination of OVs with current immunotherapies to convert “immune-cold” tumors to “immune-hot” will almost certainly improve the potency of OVs. Here, we discuss strategies that are explored to further improve oncolytic virotherapy.

scholarly journals Oncolytic Virotherapy in Solid Tumors: The Challenges and Achievements

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 588
Author(s):  
Ke-Tao Jin ◽  
Wen-Lin Du ◽  
Yu-Yao Liu ◽  
Huan-Rong Lan ◽  
Jing-Xing Si ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Tumor Antigens ◽  
Adoptive Cell Therapy ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Immunosuppressive Tumor Microenvironment ◽  
Delivery Strategies ◽  
Therapeutic Tools ◽  
Immune Checkpoint Blockers

Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed.

Public Libraries of the Vladimir and Kostroma Provinces' District Towns in the Second Half of the 19th — early 20th Century

2010 ◽  
pp. 98-101 ◽  
Author(s):  
Aleksey A. Soloviev
Keyword(s):  
20Th Century ◽  
Statistical Data ◽  
Public Libraries ◽  
17Th Century ◽  
Early 20Th Century ◽  
Native Population ◽  
History Of

On the history of the first public libraries in the province towns of Vladimirskaya and Kostromskaya provinces in the second half of the 17th century - early 20th century. The author considers main statistical data of libraries and analyses necessity and influence of these libraries and reading rooms on the native population.

ABOUT CUSTOMS BUSINESS IN TURKESTAN IN THE SECOND HALF OF THE 19th -EARLY 20th CENTURY

2020 ◽  
Vol 12 (3) ◽  
pp. 38-47
Author(s):  
Chinpulat Kurbanov ◽  
Keyword(s):  
20Th Century ◽  
Scientific Article ◽  
Early 20Th Century ◽  
The Future ◽  
History Of ◽  
Stage Development

The author in this scientific article examines the stage-by-stage development and formation of customs in Turkestan in the second half of the 19th -early 20th centuries. The author studied the history of customs in Turkestan and its role in establishing a single customs line in the future with neighboring khanates. The author focuses on the role of Russia in the establishment of a single customs line and the development of customs in Turkestan

‘... Call the Mute Artifacts to Speech’: New Essays on the History of Archeology

2018 ◽  
pp. 1274-1279
Author(s):  
Elena V. Olimpieva ◽  
Keyword(s):  
20Th Century ◽  
Comparative Method ◽  
Early 20Th Century ◽  
Historical Overview ◽  
Historical Experience ◽  
Historical Material ◽  
Manuscript Tradition ◽  
History Of ◽  
Publication Practices ◽  
Controversial Nature

The article reviews O. A. Shashkova’s ‘... Call the Mute Artifacts to Speech.’ Essays on the History of Archaeography of the 15th - Early 20th Century. Wide array of sources and broad geographical frameworks allow Shashkova to present emergence and development of Russian and European archaeography from the 15th to early 20th century intelligibly enough for educational purposes. A whole chapter is devoted to the manuscript tradition and publishing of sources before Gutenberg. When considering the formation of archaeographical tradition, the author uses comparative method. O. A. Shashkova offers a historical overview and analyzes theoretical and practical issues of archaeography. The reviewer notes the significance of the chosen topic due to a need to reconsider the development of publishing in light of modern views on archaeography and to make it accessible to students and non-professionals. She notes traditional academic approach of O. A. Shashkova to presentation of the development publication practices. The review considers the possibility of using the ‘Essays...’ in studying the history of archaeography and offers possible directions for a broader consideration of historical experience, in particular, of Novikov’s publication projects. The review notes the controversial nature of the author’s approach to systematization of her large historical material in order to consider issues concerning the study of archaeographical practices. It stresses that coverage of issues of development of methods of preparation of publications separately from its historical and practical aspects hinders successful mastering of the material by an untrained reader. It concludes that the publication has high practical value for specialists in archaeography and students.

scholarly journals Combining Oncolytic Viruses and Small Molecule Therapeutics: Mutual Benefits

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3386
Author(s):  
Bart Spiesschaert ◽  
Katharina Angerer ◽  
John Park ◽  
Guido Wollmann
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Tumor Cells ◽  
Small Molecule ◽  
Antiviral Immunity ◽  
Oncolytic Viruses ◽  
Antitumor Immune Response ◽  
Antiviral Responses ◽  
Small Molecule Therapeutics ◽  
Immunosuppressive Factors

The focus of treating cancer with oncolytic viruses (OVs) has increasingly shifted towards achieving efficacy through the induction and augmentation of an antitumor immune response. However, innate antiviral responses can limit the activity of many OVs within the tumor and several immunosuppressive factors can hamper any subsequent antitumor immune responses. In recent decades, numerous small molecule compounds that either inhibit the immunosuppressive features of tumor cells or antagonize antiviral immunity have been developed and tested for. Here we comprehensively review small molecule compounds that can achieve therapeutic synergy with OVs. We also elaborate on the mechanisms by which these treatments elicit anti-tumor effects as monotherapies and how these complement OV treatment.

scholarly journals Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Geometric Mean ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Cancer Center ◽  
Serum Samples ◽  
Humoral Immune ◽  
History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

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