scholarly journals NF-κB Signaling in Targeting Tumor Cells by Oncolytic Viruses—Therapeutic Perspectives

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 426 ◽  
Author(s):  
Justyna Struzik ◽  
Lidia Szulc-Dąbrowska
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Oncolytic Virus ◽  
Antitumor Effect ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Nuclear Factor ◽  
Protective Mechanisms ◽  
Antitumor Response ◽  
Promising Therapeutic Approach

In recent years, oncolytic virotherapy became a promising therapeutic approach, leading to the introduction of a novel generation of anticancer drugs. However, despite evoking an antitumor response, introducing an oncolytic virus (OV) to the patient is still inefficient to overcome both tumor protective mechanisms and the limitation of viral replication by the host. In cancer treatment, nuclear factor (NF)-κB has been extensively studied among important therapeutic targets. The pleiotropic nature of NF-κB transcription factor includes its involvement in immunity and tumorigenesis. Therefore, in many types of cancer, aberrant activation of NF-κB can be observed. At the same time, the activity of NF-κB can be modified by OVs, which trigger an immune response and modulate NF-κB signaling. Due to the limitation of a monotherapy exploiting OVs only, the antitumor effect can be enhanced by combining OV with NF-κB-modulating drugs. This review describes the influence of OVs on NF-κB activation in tumor cells showing NF-κB signaling as an important aspect, which should be taken into consideration when targeting tumor cells by OVs.

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 IP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivo.

1993 ◽  
Vol 178 (3) ◽  
pp. 1057-1065 ◽  
Author(s):  
A D Luster ◽  
P Leder
Keyword(s):  
Tumor Cells ◽  
Interferon Gamma ◽  
T Lymphocyte ◽  
Inflammatory Infiltrate ◽  
Antitumor Effect ◽  
Genetically Engineered ◽  
Antitumor Response ◽  
Ifn Gamma ◽  
Biologic Property

IP-10 is a member of the -C-X-C-chemokine superfamily of proinflammatory cytokines whose secretion is induced by interferon gamma (IFN-gamma) and lipopolysaccharide (LPS). To date no function has been described for IP-10. We have genetically engineered tumor cells to secrete high levels of murine IP-10 and demonstrate that while IP-10 has no effect on the growth of these tumor cells in culture, it elicits a powerful host-mediated antitumor effect in vivo. The IP-10 antitumor response is T lymphocyte dependent, non-cell autonomous, and appears to be mediated by the recruitment of an inflammatory infiltrate composed of lymphocytes, neutrophils, and monocytes. These results document an important biologic property of IP-10 and raise the possibility that some of the T cell-directed effects of IFN-gamma and LPS may be mediated by this chemokine.

scholarly journals Oncolytic Virotherapy and Microenvironment in Multiple Myeloma

2021 ◽  
Vol 22 (5) ◽  
pp. 2259
Author(s):  
Valentina Marchica ◽  
Federica Costa ◽  
Gaetano Donofrio ◽  
Nicola Giuliani
Keyword(s):  
Multiple Myeloma ◽  
Oncolytic Virus ◽  
Plasma Cells ◽  
Hematologic Malignancy ◽  
Oncolytic Viruses ◽  
New Drugs ◽  
Oncolytic Virotherapy ◽  
Antiviral Immune Response ◽  
Different Types ◽  
Human Viruses

Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of bone marrow (BM) clonal plasma cells, which are strictly dependent on the microenvironment. Despite the improvement of MM survival with the use of new drugs, MM patients still relapse and become always refractory to the treatment. The development of new therapeutic strategies targeting both tumor and microenvironment cells are necessary. Oncolytic virotherapy represent a promising approach in cancer treatment due to tumor-specific oncolysis and activation of the immune system. Different types of human viruses were checked in preclinical MM models, and the use of several viruses are currently investigated in clinical trials in MM patients. More recently, the use of alternative non-human viruses has been also highlighted in preclinical studies. This strategy could avoid the antiviral immune response of the patients against human viruses due to vaccination or natural infections, which could invalid the efficiency of virotherapy approach. In this review, we explored the effects of the main oncolytic viruses, which act through both direct and indirect mechanisms targeting myeloma and microenvironment cells inducing an anti-MM response. The efficacy of the oncolytic virus-therapy in combination with other anti-MM drugs targeting the microenvironment has been also discussed.

scholarly journals Oncolytic Viruses in Combination Therapeutic Approaches with Epigenetic Modulators: Past, Present and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2761
Author(s):  
Annalisa Chianese ◽  
Biagio Santella ◽  
Annalisa Ambrosino ◽  
Debora Stelitano ◽  
Luca Rinaldi ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Entry ◽  
Therapeutic Option ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Tumor Treatment ◽  
Therapeutic Approaches ◽  
Combination Treatments ◽  
Combination Strategies ◽  
Current Therapies

According to the World Cancer Report, cancer rates have been increased by 50% with 15 million new cases in the year 2020. Hepatocellular carcinoma (HCC) is the only one of the most common tumors to cause a huge increase in mortality with a survival rate between 40% and 70% at 5 years, due to the high relapse and limitations associated with current therapies. Despite great progress in medicine, oncological research is always looking for new therapies: different technologies have been evaluated in clinical trials and others have been already used in clinics. Among them, oncolytic virotherapy represents a therapeutic option with a widespread possibility of approaches and applications. Oncolytic viruses are naturally occurring, or are engineered, viruses characterized by the unique features of preferentially infecting, replicating, and lysing malignant tumor cells, as well as activating the immune response. The combination of oncolytic virotherapy and chemical drugs are arousing great interest in the tumor treatment. In this scenario, novel and promising anticancer therapies comprise combinations of oncolytic viruses and epigenetic modulators or inhibitors of the signalling pathways. Combination treatments are required to improve the immune response and allow viral entry, replication, and diffusion between proximal cells. In this review, we summarize all combination therapies associated with virotherapy, including co-administered inhibitors of chromatin modifiers (combination strategies) and inserted target sites for miRNAs (recombination or arming strategies).

scholarly journals Prospects for Using Expression Patterns of Paramyxovirus Receptors as Biomarkers for Oncolytic Virotherapy

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3659
Author(s):  
Olga V. Matveeva ◽  
Svetlana A. Shabalina
Keyword(s):  
Tumor Cells ◽  
Measles Virus ◽  
Sendai Virus ◽  
Expression Patterns ◽  
Malignant Cell ◽  
Oncolytic Viruses ◽  
Host Cells ◽  
Oncolytic Virotherapy ◽  
Published Data ◽  
Surface Receptors

The effectiveness of oncolytic virotherapy in cancer treatment depends on several factors, including successful virus delivery to the tumor, ability of the virus to enter the target malignant cell, virus replication, and the release of progeny virions from infected cells. The multi-stage process is influenced by the efficiency with which the virus enters host cells via specific receptors. This review describes natural and artificial receptors for two oncolytic paramyxoviruses, nonpathogenic measles, and Sendai viruses. Cell entry receptors are proteins for measles virus (MV) and sialylated glycans (sialylated glycoproteins or glycolipids/gangliosides) for Sendai virus (SeV). Accumulated published data reviewed here show different levels of expression of cell surface receptors for both viruses in different malignancies. Patients whose tumor cells have low or no expression of receptors for a specific oncolytic virus cannot be successfully treated with the virus. Recent published studies have revealed that an expression signature for immune genes is another important factor that determines the vulnerability of tumor cells to viral infection. In the future, a combination of expression signatures of immune and receptor genes could be used to find a set of oncolytic viruses that are more effective for specific malignancies.

scholarly journals Recombinant adeno-associated viruses as a gene delivery vehicle for the use in molecular medicine

2021 ◽  
Author(s):  
AV Blagov
Keyword(s):  
Immune Response ◽  
Oncolytic Virus ◽  
Therapeutic Agents ◽  
Oncolytic Viruses ◽  
Antitumor Immune Response ◽  
Molecular Medicine ◽  
Delivery Vehicle ◽  
High Prevalence ◽  
Gene Delivery Vehicle ◽  
Dual Action

Breast cancer (BC) is a cancer with a high prevalence and mortality among women worldwide. With the current diagnostics methods, BC may remain undetected at its early stages, and the therapies developed for the disease are associated with severe side effects. Oncolytic viruses can be the basis of the new, effective BC treatment approaches. The viruses destroy tumor cells directly and launch the antitumor immune response; this dual action supports their efficacy. It is possible to make the oncolytic virus therapy more effective by designing genetically modified viruses that can target BC cells better and/or induce a stronger antitumor immune response. This review outlines the directions of development of oncolytic viruses in BC treatment, covers the optimal ways of delivering viruses to the tumor and the efficacy of their use in combination with other therapeutic agents (methods) and presents the prospects of using oncolytic viruses in antitumor vaccines.

Natural Macromolecules with Protective and Antitumor Activity

2018 ◽  
Vol 18 (5) ◽  
pp. 675-683 ◽  
Author(s):  
Cioanca Oana ◽  
Trifan Adriana ◽  
Cornelia Mircea ◽  
Scripcariu Dragos ◽  
Hancianu Monica
Keyword(s):  
Immune Response ◽  
Antitumor Activity ◽  
Tumor Cells ◽  
Biological Activities ◽  
Molecular Size ◽  
Plant Lectins ◽  
Natural Toxins ◽  
Glycosidic Bonds ◽  
Novel Drug

This review summarizes the literature data regarding plant lectins as novel drug sources in the prevention or treatment of cancer. Moreover, such compounds have been described as natural toxins that possess different biological activities (cytotoxic, antitumor, antimutagenic and anticarcinogenic properties). This activity depends greatly on their structure and affinity. Most of the mushroom heterosides are known as β-glucans with β-(1→3)-glycosidic bonds. It is thought that their conformation, bonds, molecular size can modulate the immune response by triggering different receptors. The mechanism on normal and tumor cells of various plant and mushroom polysaccharides and lectins is briefly presented in this paper.

scholarly journals Evaluation of the antitumor effect of lectin obtained from the latex of Euphorbia tirucalli against tumor cells of Ehrlich

2014 ◽  
Vol 8 (S4) ◽  
Author(s):  
Aline Richter ◽  
Caroline Mota ◽  
Fernanda Santiago ◽  
Marcelo Barbosa
Keyword(s):  
Tumor Cells ◽  
Antitumor Effect ◽  
Euphorbia Tirucalli

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

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