CC BY
0JWPR
Journal of World's Poultry Research
2023, Scienceline Publication
J. World Poult. Res. 13(4): 373-385, December 25, 2023
Review Article, PII: S2322455X2300040-13 License: CC BY 4.0
DOI: https://dx.doi.org/10.36380/jwpr.2023.40
The Role of Newcastle Disease Virus in Cancer Therapy: A Systematic Review
Niloofar Rajaei1 , Navid Faraji1 , Pedram Borhani Khabaz1 © , Mohammad Yousefi © Naghmeh Layegh Khavidaki1 ©, and Alireza Omranzadeh1 ©
'Medical Doctor, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2Department of Medicine, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
Corresponding author's E-mail: omranzadeha@gmail.com
Received: 25 September 2023 Accepted: 11 November 2023
ABSTRACT
Recently, immunotherapy has become a hopeful option for cancer therapy. Taking advantage of pathogens is a well-established method of cancer immunotherapy. It has been shown that the Newcastle disease virus (NDV), an avian virus with oncolytic properties, can be used to treat cancer. This study was designed to offer a comprehensive overview of the role of NDV in cancer treatment, focusing on its attributes, mechanisms of action, preclinical and clinical trials, and future perspectives. A systematic literature review was performed to gather relevant information about NDV in cancer therapy. The inclusion criteria of this study included studies conducted in vitro and in vivo as well as clinical trials to investigate the anti-cancer effects and mechanisms behind the action of NDV. A total of 34 out of 176 academic articles, preclinical studies, clinical trials, and review articles were analyzed to collect key findings.-In addition to replicating selectively through invading cancerous cells, NDV has been shown to induce apoptosis in in vivo studies. There is evidence that it can induce apoptosis, induce oncolysis, and modulate immune function in preclinical research. Studies have demonstrated that combining this therapy with chemotherapy, immunotherapies, and targeted therapies provides encouraging results regarding effectiveness and safety in animal models. As a result of NDV's ability to induce immunogenic cell death, the immune system is activated when it reacts to cancer cells. In addition, NDV infection promotes the recruitment and activation of immune cells, especially cytotoxic T cells, by releasing cytokines and chemokines. This dual mechanism triggers anti-cancer immune responses. An interesting new approach to cancer treatment is based on the selective replication of NDV, which can induce immunogenic cell death in tumor tissues and interfere with oncogenic signaling pathways. Research in preclinical models has yielded valuable information, as well as evidence of the effectiveness and safety of clinical trials. A synergistic effect has been demonstrated when chemotherapy, immunotherapies, and targeted therapies are used in conjunction.
Keywords: Cancer, Immune responses, Newcastle disease, Targeted therapy
To treat cancer effectively, there is a constant demand for innovative and reliable treatment methods worldwide (Cheng et al., 2021; Asouli et al., 2023; Sadr et al., 2023a). A variety of cancer treatments, such as chemotherapy, surgery, and radiotherapy, have made substantial progress in recent years (Butler et al., 2021; Debela et al., 2021; Wang et al., 2021; Sadr et al., 2023b). The problem is that common treatments such as chemotherapy, surgery, and
radiotherapy possess toxicities, resistance capabilities, and impermeability in the presence of cancer cells (Zhao et al., 2023). Therefore, it is imperative to develop novel approaches for detecting tumor cells and killing them with minimal damage to healthy tissues (Hajjafari et al., 2022; Saeed et al., 2022; Sadr et al., 2023c). A new field of investigation is the study of oncolytic virotherapy, in which viruses are used as cancer-fighting agents (Zheng et al., 2019; Nakao et al., 2020; Cheng et al., 2022). A virus is considered oncolytic if it is engineered or naturally
To cite this paper: Rajaei N, Faraji N, Khabaz PB, Yousefi M, Khavidaki NL, and Omranzadeh A (2023). The Role of Newcastle Disease Virus in Cancer Therapy: A Systematic Review. J. World Poult. Res., 13(4): 373-385. DOI: https://dx.doi.org/10.36380/jwpr.2023.40
occurs with the ability to selectively infect and destruct neoplastic cells, thereby regressing tumors (Lin et al., 2023). It is the inherent mechanisms of viruses that permit them to replicate in cancer cells selectively and lead to the death of the tumor cells without affecting healthy cells, providing a promising approach (Kooti et al., 2021; Ghasemi Darestani et al., 2023).
Known as a member of the Paramyxoviridae family, the Newcastle disease virus (NDV) has recently been considered an option for cancer therapy (Zamarin and Palese, 2012; Cheng et al., 2016). Various bird species are affected by NDV, leading to mild to severe symptoms of respiratory infections and neurological disorders. The NDV, however, can kill a wide range of human neoplastic cells, such as hematological malignancies and solid tumors (Russell, 2002; Cuadrado-Castano et al., 2015).
The NDV's distinctive features make it a suitable choice for oncolytic virotherapy (Garmaroudi et al., 2022). Within tumor cells, NDV replicates preferentially due to modifications of the signaling pathways within the cells and weakened antiviral defenses (Shao et al., 2019; Palanivelu et al., 2023). Furthermore, NDV can trigger immunogenic cell death, thereby increasing the efficacy of NDV by enhancing the immune system's ability to fight cancer (Buijs et al., 2015; Koks et al., 2015). NDV has received considerable attention due to these properties in terms of its efficacy as a cancer treatment approach (Apostolidis et al., 2007; Song et al., 2019).
The main objective of the current review is to summarize the clinical and preclinical research designed to assess the therapeutic potential of NDV in various cancer types. Through a thorough review of the existing data, the review looks at the oncolytic characteristics of NDV, underlying mechanisms, safety risks, and efficiency. Clinical and preclinical studies are both involved. Additionally, this study aimed to investigate the molecular processes behind NDV's anti-cancer activities, such as its interaction with neoplastic cells and the microenvironment surrounding tumors.
METHODOLOGY AND SEARCH STRATEGY
A contemporary perspective has been included in the review by taking into account studies that were published from 2000 to 2023. An extensive search strategy was employed across multiple databases, including Scopus, Embase, PubMed, and Web of Science, in order to initiate the review process. Several search terms were used, including "Newcastle Disease Virus," "NDV," "cancer therapy," "oncolytic virotherapy," and "oncolytic viruses." Boolean operators (AND, OR) were used with appropriate
truncations to assure coverage of all relevant terms (Karimi et al., 2010).
Several inclusion criteria were established in order to include in vitro and in vivo studies along with a clinical trial, and this is aimed at assessing NDV's anti-cancer properties and unraveling its mechanisms of action. The current study was applied to the selection of studies specifically focusing on the therapeutic effects of NDV in cancer treatment. It is intended to limit the publication of in vitro and animal models, as well as clinical trials, to publications in English. Focusing on recent developments, a detailed description of study characteristics such as the authors, study year, study design, cancer type, NDV strains employed, participant populations, methodologies, major findings, and the outcome of cancer therapy were extracted. This systematic approach allows for the extraction of consistent data from multiple studies. The exclusion criteria for the study included any viruses other than NDV, and these viruses were specifically excluded from the analysis.
OVERVIEW OF NEWCASTLE DISEASE VIRUS
Characteristics of Newcastle disease virus
As one of the members of the Paramyxoviridae family, NDV belongs to the Avulavirus genus (Suarez et al., 2020). NDV is a single-stranded RNA virus, which is highly contagious among avian species (Getabalew et al., 2019; Behboudi and Hamidi Sofiani, 2021). Various hosts have been identified for NDV infection, including poultry, wild birds, and rarely mammals, like humans (Ashraf and Shah, 2014; Ul-Rahman et al., 2022). Electron microscopy indicates that the virus displays a pleomorphic morphology with filamentous or spherical particles (Rush et al., 2020). Oncolytic virotherapy presents a potential application of NDV because of its special capabilities, such as directly killing tumor cells and stopping angiogenesis (Bello et al., 2020). Mononegavirales viruses are non-segmented and have an envelope (Samal, 2021). NVD contains a negative-sense RNA genome encoding six main structural proteins, including matrix proteins (Ms), phosphoproteins (Ps), hemagglutinin-neuraminidase proteins (HNs), nucleoproteins (NPs), fusion proteins (Fs), and large polymerase proteins (Chen et al., 2015). Viruses and their hosts' replication, assembly, and interaction depend on these proteins.
Newcastle disease virus strains and oncolytic properties
Based on their virulence in poultry, several strains of NDV are categorized into distinct pathotypes (Choi et al.,
2013; Fentie et al., 2014; Dimitrov et al., 2016). The most common strain types are velogenic (highly virulent), mesogenic (moderately virulent), and lentogenic (avirulent) (Liu et al., 2007a). Several strains of NDV have demonstrated oncolytic properties, namely the ability to target and destroy cancerous cells (Davis and Fang, 2005; Everts and van der Poel, 2005). It has been extensively studied that a number of NDV strains exhibit the ability to treat cancer partly by selectively replicating only in tumor cells without causing harm to the normal cells (Howells et al., 2017). By exploiting the tumor microenvironment, NDV takes advantage of the unique properties of tumor cells to multiply and cause cell death, namely dysfunctional signaling pathways of interferons, impaired antiviral defenses, and altered surface proteins (Zhao et al., 2012).
Mechanisms of Newcastle disease virus-induced oncolysis
The entry of virus, reproduction, transmission, and triggering death of cancer cells are all steps in the oncolytic process of NDV. The following are some processes that contribute to oncolysis induced by NDV. As soon as NDV reaches the surface of the cancer cells, it binds to specific receptors on the cell surface (Meng et al., 2021). NDV uses sialic acid as its main receptor, which is commonly present in most cancer cells (Matveeva et al.,
2015). NDV multiplies itself by injecting genomic RNA into the cytoplasm of its host (Fournier and Schirrmacher, 2013). When viral RNA is translated and replicated, it produces viral proteins and virus particles, which are the byproducts of viral RNA transcription and replication (Randall and Goodbourn, 2008). Via fusion between infected and non-infected cells, an NDV infection forms multinucleated giant cells known as syncytial cells (Krabbe and Altomonte, 2018; Dittmar et al., 2021). Apart from facilitating the virus' spread through tumors, syncytia also enhances the virus' oncolytic activity (Sasso et al., 2020).
The NDV infection stimulates a wide range of innate immune responses, including the release of cytokines and type I interferons (IFNs) (Fournier et al., 2012). These responses have a positive outcome, which is a greater immune reaction towards neoplastic cells since immune cells become activated and recruited. One of the most prominent mechanisms involved in NDV-induced oncolysis is apoptosis, which leads to cell membrane shrinkage, cellular DNA fragmentation, and cell membrane blebbing (Ali et al., 2011; Schirrmacher, 2022a). Tumor cells undergo apoptosis when NDV triggers cell death pathways. Moreover, NDV infection can also lead to necrotic cell death in some cases (Mohammed et al., 2019) (Figure 1).
n 1 f ;
Figure 1. The various mechanisms by which the Newcastle Disease Virus (NDV) induces cell death in cancer cells upon binding to cancer cell receptors. It involves the activation of T cells, Natural Killer (NK) cells, and macrophages, as well as the initiation of apoptosis, necrosis, and pyroptosis pathways (Dendritic cells [DC] play crucial roles in this process).
PRECLINICAL STUDIES
In vitro studies evaluating Newcastle disease virus's anti-cancer effects
To better understand NDV mechanisms and their potential anti-cancer effects, in vitro experiments have been undertaken utilizing various cancer cell lines. In these investigations, various techniques are frequently employed to determine whether NDV is cytotoxic, if it replicates within cells, and how it influences cellular interaction (Sánchez et al., 2015; Yurchenko et al., 2018).
The 3 -(4,5 -dimethylthiazol-2 -yl)-2,5-
diphenyltetrazolium bromide assay (MTT) estimates the functions of mitochondria, whereas the trypan blue exclusion assay determines the integrity of the cell membrane (Ghorbankhani et al., 2023). MTT is commonly used for the assessment of cytotoxicity and viability of cells. These tests allow the quantification of NDV and its efficiency of viral replication via multiple cell lines to determine how it affects tumor cell viability (Jagtap et al., 2017).
Moreover, researchers have attempted to identify how NDV induces oncolysis. Changes in cell morphology and DNA fragmentation initiate apoptotic pathways (Elankumaran et al., 2006). A variety of methods are used to detect apoptosis markers, including Bcl-2 proteins, caspases, and DNA damage markers, utilizing different techniques, such as immunoblotting, flow cytometry, and immunofluorescence (Nirmala and Lopus, 2020; Kari et al., 2022).
Additionally, researchers have studied NDV's immunomodulatory abilities in vitro alongside its oncolytic properties (Yang et al., 2021; Hu et al., 2022). Cytokines and chemokines released during infection with NDV have been shown to induce immune cells' recruitment and activation when co-culturing with cancer cells (Tang et al., 2022). In many studies, it has been noted that NDV induces the expression of Major Histocompatibility Complex (MHC) molecules in addition to co-stimulatory molecules, which are involved in presenting antigens and activating immune cells (Burman et al., 2020; Schirrmacher et al., 2022b).
Animal models and their relevance to human cancers
A key part of evaluating NDV in cancer therapy is testing its performance and safety in animal models (bin Umair et al., 2022). Consequently, the oncolytic effects of the virus, its capability of inhibiting tumor growth and metastasis, as well as its tendency to interact with the
immune system can be investigated by researchers (Li et al., 2022). Animal models need to be selected considering the purpose of the research, the type of cancer, and the available options (e.g., transgenic or xenograft models). Various animal models have been utilized to examine the effects of implanting human cancer cells into mice with immune deficiencies (Fang et al., 2023).
In addition to evaluating NDV's oncolytic effects in vivo, it is also possible to assess tumor regression and virus replication at tumor sites, along with effects on normal tissues (Rius-Rocabert et al., 2020; Kalafati et al., 2023; Sadri et al., 2023). Monitoring tumor growth involves calipers or non-invasive imaging methods like positron emission tomography (PET) or bioluminescence (O'farrell et al., 2013).
It is also possible to explore the therapeutic potential of NDV using genetically modified mice (GEMMs) with spontaneous tumor development (Chen et al., 2022; Tornesello et al., 2022). Several characteristics of these models are similar to those of human cancer, including tumor heterogeneity, stromal interactions, and immune responses. GEMMs offer a more physiologically appropriate way of investigating NDV's effects on cancer growth, metastasis, and immune reactions (Zeng et al., 2021).
Additionally, animal models have been employed to visualize tumor attributes and track treatment efficacy, and NDV biodistribution was assessed by Magnetic Resonance Imaging (MRI) and Positron Emission Tomography-Computed Tomography (PET-CT) (Pierce et al., 2021; Siafaka and Gundogdu, 2023).
Although animal models cannot completely mimic the complexities of cancers in humans, adequately designed and carefully conducted studies can provide valuable preclinical information for advancements in NDV therapy and the development of clinical trials in humans (Prestwich et al., 2008; Wollmann et al., 2012).
Safety and toxicity profiles
It is paramount to assess the safety and toxicity profiles of NDV in preclinical studies before clinical trials to ensure patient safety. Several studies are being carried out on NDV in order to identify potential side effects, measure its maximum tolerated dose (MTD), and develop safety protocols for human application (Lorence et al., 2007; Koppers-Lalic and Hoeben, 2011; Abdullahi et al., 2018). The animals are closely monitored for signs of distress, behavioral changes, weight fluctuations, and any changes in vital signs. Hematological and
histopathological analyses and blood chemistry tests are carried out to assess NDV's toxicity (Kadhim et al., 2022).
Moreover, viral shedding and off-target effects are particularly assessed. The researchers may examine how long and how much NDV reproduces in non-tumor tissues if it can infect them (Everts and van der Poel, 2005). This type is evaluated to determine dosage and treatment schedules and identify potential risks associated with systemic administration (Yu et al., 2022). In addition to assessing potential drug interactions, preclinical studies are intended to determine whether NDV interacts with
other medications. To enhance cancer treatment's success, chemotherapy, radiotherapy, and immunotherapy are often administered together (Yaghoubi et al., 2019). A comprehensive analysis of the safety and tolerability profiles of NDV-based therapies in preclinical studies allows for the safe translation of NDV-based therapies to the clinic (Al-Shammari et al., 2021; Al-Shammari et al., 2020). As a result, patients can be guided on the best dosing regimens and treatment strategies to suit their needs. This can be a safe and reliable method with minimal side effects (Figure 2).
Figure 2. The activation of the immune system by Newcastle virus. The virus enters the cancer cell, triggering the activation of APC cells. Subsequently, CD8+ T cells become activated, and these immune cells lead to the cancer cell's death. APC: Antigen presenting cell, CTLA-4L: Cytotoxic T-lymphocyte associated protein 4, MHC: Major histocompatibility complex, IFN: Interferon, TAAs: Tumor associated antigens, PAMP: Pathogen associated molecular pattern, DAMP: Damage associated molecular pattern, PDL 1: Programmed death ligand-1
CLINICAL TRIAL PHASES
The use of the NDV for killing cancer cells has been successfully demonstrated in both in vitro and in vivo stages. Now, it needs to be investigated in clinical trials, and so far, a few clinical studies have been conducted. Freeman et al. (2006) and Lam et al. (2011) conducted
phase I clinical trials as the first step in evaluating NDV for cancer therapy regarding safety, dosage, and effectiveness (Freeman et al., 2006; Lam et al., 2011). A few patients are involved in these studies, which mostly attempt to determine the MTD and identify adverse effects restricting its usage.
A Phase I study administers NDV via various routes, particularly intratumoral injection, intravenous injection, and intranasal injection, to identify its optimal delivery method and safety status (Malogolovkin et al., 2021). A high degree of homogeneity is guaranteed by setting criteria for patients' eligibility based on tumor type, stage of disease, and previous treatment history (Taguchi et al., 2017). Potential adverse events are identified in Phase I trials, the MTD is determined, and the recommended Phase II dose (Laurie et al., 2006). As secondary endpoints, NDV may also be evaluated for its pharmacokinetics and pharmacodynamics (PD), assessed for tumor responses with imaging techniques, and explored for preliminary anti-tumor activity (Liu et al., 2007b). Phase 1 of the study has yielded promising outcomes; however, it is imperative to underscore that these positive results constitute merely a preliminary step in a more extensive and intricate scientific investigation. Subsequent phases, notably Phases 2 and 3, demand rigorous scrutiny and thorough exploration to elucidate further insights, address potential limitations.
COMBINATION STRATEGIES
Combination with chemotherapy agents
Research indicates that NDV, combined with chemotherapy drugs, can enhance cancer treatment outcomes (Jiang et al., 2014). It is based on the potential synergistic effects of both oncolysis induced by NDV and cytotoxicity caused by chemotherapy that justify the use of these medications together (Al-Shammari et al., 2019).
Several mechanisms have been demonstrated in preclinical studies to sensitize cancer cells to chemotherapy by NDV (Zhu et al., 2021; Faranoush et al., 2023). When cancer cells become infected with NDV, they are more susceptible to chemotherapy agents that induce apoptosis, such as caspases, Bax, and Bak (Cuadrado-Castano et al., 2015). Additionally, NDV-induced immunogenic cell death can activate an immune response that enhances chemotherapy effectiveness through tumor-specific antigen release. Furthermore, NDV may be able to overcome chemotherapy resistance. Multiple drug resistance has been associated with its modulation of P-glycoprotein (P-gp) (Garg et al., 2015; Kadhim et al., 2022). The NDV counteracts chemotherapy drug resistance by inhibiting these transporters, which allows drug concentrations to increase inside the cell.
NDV, in conjunction with chemotherapy, appears to have promising results in clinical trials (Cross and Burmester, 2006; Ripp et al., 2022). Many of these trials require determining the most appropriate sequence,
dosage, and treatment timing. These combinations improved the progression-free survival rate, overall survival rate, and response rates in several types of cancer, including pancreatic cancer, lung cancer, and ovarian cancer (Turnis et al., 2015).
Combination with immunotherapies
In order to enhance anti-tumor immune responses, NDV can be combined with immunotherapies, such as adoptive cell therapies or immune checkpoint inhibitors (Marchini et al., 2016). NDV is an ideal co-therapeutic agent for cancer standard medications because it induces immunogenic cell death and stimulates tumor antigen release. NDV combined with immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, strengthened the immune reaction against tumors in several preclinical experiments (Zamarin et al., 2014; Hwang et al., 2020). As a result of virus infection, immune checkpoint molecules are expressed more highly within cancer cells, increasing their susceptibility to immune checkpoint blockade. Further, NDV-induced release of tumor antigens can broaden the range of immune targets for immune checkpoint inhibitors, enhancing their effectiveness (Burman et al., 2020; Chiu et al., 2020).
It has also been shown that NDV can be used in conjunction with adoptive cell therapies, like Chimeric Antigen Receptor (CAR) T-cell (Bahmanyar et al., 2022). Infection with NDV can increase the expression of tumor-associated antigens on cancer cells, making them more recognizable and susceptible to CAR T-cell therapy (Mardi et al., 2022). Furthermore, NDV can induce immunogenic cell death, causing a pro-inflammatory microenvironment supporting adopting T cells' activation and persistence (Ajina and Maher, 2017; Rezaei et al., 2022).
Combination with targeted therapies
By combining NDV with targeted cancer treatments, such as monoclonal antibodies and tyrosine kinase inhibitors (TKIs), more effective treatment can be achieved (Zhu et al., 2021). Targeted therapies can specifically inhibit molecular targets or aberrant signaling pathways that contribute to tumor growth and survival.
Preclinical studies have demonstrated several mechanisms demonstrating how NDV can enhance targeted therapies' anti-tumor effects. Signaling pathways such as VEGF, HER2, or EGFR can be modulated by NDV infection (Howells et al., 2017; Ali et al., 2021). These pathways are commonly targeted by TKIs or monoclonal antibodies. With targeted therapies, NDV
inhibits tumor cell proliferation, induces apoptosis, and suppresses angiogenesis (Zhang and Cheng, 2020; Tian et al., 2022).
In combination with targeted therapies, NDV has demonstrated acceptable results in cancer types, including
melanoma, breast cancer, and colorectal cancer (Markman and Shiao, 2015). It is essential to study the safety profiles of treatment options, determine the most beneficial treatments, and determine the most appropriate treatment schedule (Figure 3).
Figure 3. Recombinant Newcastle disease virus is a modified form of the Newcastle disease virus that has been engineered for various therapeutic and immunotherapeutic applications. It is known to activate cytotoxic T cells and induce the secretion of cytokines and chemokines from antigen-presenting cells, such as dendritic cells.
FUTURE DIRECTIONS AND CHALLENGES Emerging research and novel applications
NDV investigation is being carried out to discover new applications for this virus and examine its potential in cancer therapy. Incorporating newly developed targeted therapies, radiotherapy, and epigenetic modulators into NDV is being studied (de Graaf et al., 2018). It is possible to enhance the anti-tumor effects of NDV through these combinations so as to circumvent potential resistance mechanisms and further improve its effectiveness (Oladejo et al., 2022). Using genetic engineering methods, NDVs with enhanced therapeutic properties are created (Everts and van der Poel, 2005; Kaufman et al., 2015). Therefore, it is possible to modify NDV so that tumor selectivity is improved, replication efficiency increases or therapeutic
components are included to enhance anti-cancer activity (Howells et al., 2017; Zhu et al., 2021). It is modifying immune responses to enhance anti-tumor immunity triggered by NDV. It is necessary to boost the immune system in order to overcome immunosuppression caused by tumor microenvironment using cytokines, immune checkpoint inhibitors, or other immunomodulators in conjunction with NDV (Locy et al., 2018; Vijayakumar et al., 2020).
Facilitating the delivery of NDV directly to tumor cells while minimizing adverse effects (Raja et al., 2018; Scott et al., 2018). For instance, viral vectors, nanoparticles, and specific targeting ligands are capable of improving therapeutic performance and tumor targeting (Kontermann et al., 2021).
Addressing limitations
Achieving optimal results of NDV-based therapeutic plans calls for dealing with several limitations and challenges.: Optimizing NDV-based therapies with consideration of tumor heterogeneity as well as individualized patient profiles. Discovering and disabling immune evasion pathways cancer cells use to escape NDV-induced immune reactions (Twumasi-Boateng et al., 2018; Abdou et al., 2022). NDV can be combined with immune checkpoint inhibitors, immune stimulators, or innovative immunotherapeutic methods to increase the immune response against cancer (Moehler et al., 2016; Shaver et al., 2021). They establish the most appropriate dose, timetable, and delivery method for NDV-based treatments. Several factors are considered, such as the dose of the virus, the type and stage of the disease, the frequency with which the drug is administered, and the possibility of drug interactions (Farkona et al., 2016; Schirrmacher, 2020). They assess NDV's safety parameters across different patient groups and consider possible concerns like systemic toxicity, viral shedding, and long-term consequences (Vile et al., 2002). The monitoring and reporting of adverse reactions are essential to evaluating the safety of therapeutic interventions based on NDVs and complying with regulations and guidelines to receive approval for NDV-based medical applications (Jafari et al., 2022). Maintain compliance with regulatory requirements for NDV-based therapies, as well as facilitating their translation into standard clinical practice through awareness of the regulatory framework (Ricca et al., 2018; Burke et al., 2020; Svensson-Arvelund et al., 2022). Having a strategy for commercializing and an analysis of the economic feasibility is also imperative for NDV-based treatments to be widely adopted and accessible. Challenges such as these must be overcome, and research in these areas must progress in order for NDV-based therapies to become a mainstream treatment option for cancer and provide better results for patients. In order to overcome these challenges, collaboration is required among clinicians, scientists, regulatory authorities, and industry constituencies.
CONCLUSION
This review highlights the growing prominence of oncolytic virotherapy utilizing NDV in cancer treatment, underscoring its ability to replicate within tumor cells selectively, trigger immunogenic cell death, and influence
oncogenic signaling pathways, as supported by various in vivo and in vitro studies.
Numerous clinical trials have been undertaken at the NDV site, assessing its safety, effectiveness, and use in combined strategies for cancer treatment. Although these advances have been made, several challenges remain, including immune escape mechanisms, tumor heterogeneity, and tailoring treatment options according to tumor traits. In addition, treatments based on NDV require careful consideration of both regulatory and commercialization issues in order for them to become widely available and accepted. The potential of NDV in cancer therapy is considerable. A combination of oncolytic virotherapy, cell death induced by immunogenic factors, and alteration of oncogenic signaling pathways is at the core of this innovative approach. However, it's crucial to acknowledge that the clinical translation of NDV-based oncolytic virotherapy may face challenges such as optimizing delivery methods, addressing potential offtarget effects, and ensuring its safety and efficacy in human subjects, which require further research and development. NDV-based treatments are expected to revolutionize cancer treatment, improve patient outcomes, and allow for more individualized and precise cancer treatments by conducting further research, collaborating, and addressing challenges in the future.
DECLARATIONS
Authors' contribution
Alireza Omranzadeh conceptualized the study, while all authors contributed to the methodology, formal analysis, and investigation. The original draft was a collaborative effort, with all authors involved in writing, reviewing, and editing. All authors approved the final version of the manuscript for publication in the journal.
Ethical consideration
Ethical issues, such as data fabrication, double publication and submission, redundancy, plagiarism, consent to publish, and misconduct, have been checked by all the authors before publication in this journal.
Availability of data and materials
The datasets generated during the current study, on a reasonable request, are available from the corresponding author.
Funding
No funds were received.
Acknowledgments
Not applicable.
Conflict of interests
All of the authors declare no conflict of interest.
REFERENCES
Abdou Y, Goudarzi A, Yu JX, Upadhaya S, Vincent B, and Carey LA (2022). Immunotherapy in triple negative breast cancer: beyond checkpoint inhibitors. npj Breast Cancer, 8(1): 121. DOI: https://www.doi.org/10.1038/s41523-022-00486-y
Abdullahi S, Jäkel M, Behrend SJ, Steiger K, Topping G, Krabbe T, Colombo A, Sandiq V, Schiergens TS, Thasler WE et al. (2018). A novel chimeric oncolytic virus vector for improved safety and efficacy as a platform for the treatment of hepatocellular carcinoma. Journal of Virology, 92(23): 1386-1318. DOI: https://www.doi.org/10.1128/JVI.01386-18
Ajina A and Maher J (2017). Prospects for combined use of oncolytic viruses and CAR T-cells. Journal for Immunotherapy of Cancer, 5(1): 90. DOI: https://www.doi.org/10.1186/s40425-017-0294-6
Al-Shammari AM, Abdullah AH, Allami ZM, and Yaseen NY (2019). 2-Deoxyglucose and Newcastle disease virus synergize to kill breast cancer cells by inhibition of glycolysis pathway through glyceraldehyde3-phosphate downregulation. Frontiers in Molecular Biosciences, 6: 90. DOI:
https://www.doi.org/10.3389/fmolb.2019.00090
Al-Shammari AM, Abo-Altemen RA, Shawkat MS, and Cyperus rotundus L (2021). Alkaloid extracts enhance oncolytic Newcastle disease virus against digestive system neoplasms. South African Journal of Botany, 143: 266-273. DOI:
https://www.doi.org/10.1016/j.sajb.2021.08.002
Al-Shammari AM, Jalill RDA, and Hussein MF (2020). Combined therapy of oncolytic Newcastle disease virus and rhizomes extract of Rheum ribes enhances cancer virotherapy in vitro and in vivo. Molecular Biology Reports, 47(3): 1691-1702. DOI: https://www.doi.org/10.1007/s11033-020-05259-z
Ali R, Alabsi AM, Ali AM, Ideris A, Omar AR, Yusoff K, and Seif-Ali R (2011). Cytolytic effects and apoptosis induction of Newcastle disease virus strain AF2240 on anaplastic astrocytoma brain tumor cell line. Neurochemical Research, 36: 2051-2062. DOI: https://www.doi.org/10.1007/s11064-011-0529-8
Ali S, Xia Q, Muhammad T, Liu L, Meng X, Bars-Cortina D, Khan AA, Huang Y, and Dong L (2021). Glioblastoma therapy: Rationale for a mesenchymal stem cell-based vehicle to carry recombinant viruses, Stem Cell Reviews and Reports, 18: 523-543. DOI: https://www.doi.org/10.1007/s12015-021-10207-w
Apostolidis L, Schirrmacher V, and Fournier P (2007). Host mediated antitumor effect of oncolytic Newcastle disease virus after locoregional application. International Journal of Oncology, 31(5): 1009-1019. DOI: https://www.doi.org/10.3892/ijo.31.5.1009
Ashraf A and Shah M (2014). Newcastle disease: Present status and future challenges for developing countries. African Journal of Microbiology Research, 8(5): 411-416. DOI: https://www.doi.org/10.5897/AJMR2013.6540
Asouli A, Sadr S, Mohebalian H, and Borji H (2023). Anti-tumor effect of protoscolex hydatid cyst somatic antigen on inhibition cell growth of K562. Acta Parasitologica, 68: 385-392. DOI: https://www.doi.org/10.1007/s11686-023-00680-3
Bahmanyar M, Vakil MK, Al-Awsi GRL, Kouhpayeh SA, Mansoori H, Mansoori Y, Salehi A, Nikfar G, Tavassoli A, Behmard E et al. (2022). Opportunities and obstacles for the melanoma immunotherapy using T cell and chimeric antigen receptor T (CAR-
T) applications: A literature review. Molecular Biology Reports, 49(11): 10627-10633. DOI: https://www.doi.org/10.1007/s11033-022-07633-5
Behboudi E and Hamidi Sofiani V (2021). Immune responses to Newcastle disease virus as a minor zoonotic viral agent. Journal of Zoonotic Diseases, 5(4): 12-23. DOI:
https://www.doi.org/10.22034/jzd.2021.14024
Bello MB ,Yusoff K, Ideris A, Hair-Bejo M, Jibril AH, Peeters BP, and Omar AR (2020). Exploring the prospects of engineered Newcastle disease virus in modern vaccinology. Viruses, 12(4): 451. DOI: https://www.doi.org/10.3390/v12040451
bin Umair M, Akusa FN, Kashif H, Fatima S, Butt F, Azhar M, Munir I, Ahmed M, Khalil W, Sharyar H et al. (2022). Viruses as tools in gene therapy, vaccine development, and cancer treatment. Archives of Virology, 167(6): 1387-1404. DOI:
https://www.doi.org/10.1007/s00705-022-05432-8
Buijs PR Verhagen JH, van Eijck CH, and van den Hoogen BG (2015). Oncolytic viruses: From bench to bedside with a focus on safety. Human Vaccines & Immunotherapeutics, 11(7): 1573-1584. DOI: https://www.doi.org/10.1080/21645515.2015.1037058
Burke S, Shergold A, Elder MJ, Whitworth J, Cheng X, Jin H, Wilkinson RW, Harper J, and Carroll DK (2020). Oncolytic Newcastle disease virus activation of the innate immune response and priming of antitumor adaptive responses in vitro. Cancer Immunology, Immunotherapy, 69: 1015-1027. DOI:
https://www.doi.org/10.1007/s00262-020-02495-x
Burman B, Pesci G, and Zamarin D (2020). Newcastle disease virus at the forefront of cancer immunotherapy. Cancers, 12(12): 3552. DOI: https://www.doi.org/10.3390/cancers12123552
Butler E, Ludwig K, Pacenta HL, Klesse LJ, Watt TC, and Laetsch TW
(2021). Recent progress in the treatment of cancer in children. CA: A Cancer Journal for Clinicians, 71(4): 315-332. DOI: https://www.doi.org/10.3322/caac.21665
Chen XQ, Li ZB, Hu GX, Gu SZ, Zhang S, Ying Y, and Gao F (2015). Isolation, identification, and sequencing of a goose-derived Newcastle disease virus and determination of its pathogenicity. Avian Diseases, 59(2): 235-243. DOI:
https://www.doi.org/10.1637/10957-100914-Reg
Chen XT, Dai SY, Zhan Y, Yang R, Chen DQ, Li Y, Zhou E, and Dong R
(2022). Progress of oncolytic virotherapy for neuroblastoma. Frontiers in Pediatrics, 10: 1055729. DOI: https://www.doi.org/10.3389/fped.2022.1055729
Cheng G, Dong H, Yang C, Liu Y, Wu Y, Zhu L, Tong X, and Wang S (2021). A review on the advances and challenges of immunotherapy for head and neck cancer. Cancer Cell International, 21(1): 406. DOI: https://www.doi.org/10.1186/s12935-021-02024-5
Cheng K, Zhang H, Guo Q, Zhai P, Zhou Y, Yang W, Lu Y, Shen Z, and Wu H (2022). Emerging trends and research foci of oncolytic virotherapy for central nervous system tumors: A bibliometric study. Frontiers in Immunology, 13: 975695. DOI: https://www.doi.org/10.3389/fimmu.2022.975695
Cheng X, Wang W, Xu Q, Harper J, Carroll D, Galinski MS, Suzich J, and Jin H (2016). Genetic modification of oncolytic Newcastle disease virus for cancer therapy. Journal of Virology, 90(11): 5343-5352. DOI: https://www.doi.org/10.1128/JVI.00136-16
Chiu M, Armstrong EJL, Jennings V, Foo S, Crespo-Rodriguez E, Bozhanova G, Patin EC, McLaughlin M, Mansfeild D, Baker G et al. (2020). Combination therapy with oncolytic viruses and immune checkpoint inhibitors. Expert Opinion on Biological Therapy, 20(6): 635-652. DOI: https://www.doi.org/10.1080/14712598.2020.1729351
Choi KS, Kye SJ, Kim JY, Damasco VR Sorn S, Choi JG, Lee YJ, Kang H, Kim K, Song B et al. (2013). Molecular epidemiological investigation of velogenic Newcastle disease viruses from village chickens in Cambodia. Virus Genes, 47: 244-249. DOI: https://www.doi.org/10.1007/s11262-013-0930-2
Cross D and Burmester JK (2006). Gene therapy for cancer treatment: Past, present and future. Clinical Medicine & Research, 4(3): 218227. DOI: https://www.doi.Org/10.3121/cmr.4.3.218
Cuadrado-Castano S , Sanchez-Aparicio MT, García-Sastre A, and Villar E (2015). The therapeutic effect of death: Newcastle disease virus and its anti-tumor potential. Virus Research, 209: 56-66. DOI: https://www.doi.org/10.1016/j .virusres.2015.07.001
Davis JJ and Fang B (2005). Oncolytic virotherapy for cancer treatment: Challenges and solutions. The Journal of Gene Medicine, 7(11): 1380-1389. DOI: https://www.doi.org/10.1002/jgm.800
de Graaf J, de Vor L, Fouchier R, and Van Den Hoogen B (2018). Armed oncolytic viruses: A kick-start for anti-tumor immunity. Cytokine & Growth Factor Reviews, 41: 28-39. DOI: https://www.doi.org/10.1016/j .cytogfr.2018.03.006
Debela DT, Muzazu SG, Heraro KD, Ndalama MT, Mesele BW, Haile DC, Kituo SK, and Manyazewal T (2021). New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Medicine, 9: 20503121. DOI:
https://www.doi.org/10.1177/20503121211034366
Dimitrov KM, Ramey AM, Qiu X, Bahl J, and Afonso CL (2016). Temporal, geographic, and host distribution of avian paramyxovirus 1 (Newcastle disease virus). Infection, Genetics and Evolution, 39: 22-34. DOI: https://www.doi.org/10.1016/j.meegid.2016.01.008
Dittmar T, Weiler J, Luo T, and Hass R (2021). Cell-cell fusion mediated by viruses and HERV-derived fusogens in cancer initiation and progression. Cancers, 13(21): 5363. DOI: https://www.doi.org/10.3390/cancers13215363
Elankumaran S, Rockemann D, and Samal SK (2006). Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death. Journal of Virology, 80(15): 7522-7534. DOI: https://www.doi.org/10.1128/JVI.00241-06
Everts B and van der Poel HG (2005). Replication-selective oncolytic viruses in the treatment of cancer. Cancer Gene Therapy, 12(2): 141-161. DOI: https://www.doi.org/10.1038/sj.cgt.7700771
Fang C, Xiao G, Wang T, Song L, Peng B, Xu B, and Zhang K (2023). Emerging nano-/biotechnology drives oncolytic virus-activated and combined cancer immunotherapy. Research, 6: 0108. DOI: https://www.doi.org/10.34133/research.0108
Faranoush P, Jahandideh A, Nekouian R, and Mortazavi P (2023). Evaluation of the in vitro and in vivo effect of liposomal doxorubicin along with oncolytic Newcastle disease virus on 4T1 cell line: Animal preclinical research. Veterinary Medicine and Science, 9(3): 1426-1437. DOI:
https://www.doi.org/10.1002/vms3.1109
Farkona S, Diamandis EP, and Blasutig IM (2016). Cancer immunotherapy: The beginning of the end of cancer?. BMC Medicine, 14(1): 73. DOI: https://www.doi.org/10.1186/s12916-016-0623-5
Fentie T, Heidari A, Aiello R, Kassa T, Capua I, Cattoli G, and Sahle M (2014). Molecular characterization of Newcastle disease viruses isolated from rural chicken in northwest Ethiopia reveals the circulation of three distinct genotypes in the country. Tropical Animal Health and Production, 46: 299-304. DOI: https://www.doi .org/10.1007/s11250-013-0487-z
Fournier P, Arnold A, Wilden H, and Schirrmacher V (2012). Newcastle disease virus induces pro-inflammatory conditions and type I interferon for counter-acting Treg activity. International Journal of Oncology, 40(3): 840-850. DOI:
https://www.doi.org/10.3892/ijo.2011.1265
Fournier P and Schirrmacher V (2013). Oncolytic Newcastle disease virus as cutting edge between tumor and host. Biology, 2(3): 936-975. DOI: https://www.doi.org/10.3390/biology2030936
Freeman AI, Zakay-Rones Z, Gomori JM, Linetsky E, Rasooly L, Greenbaum E, Yair SR, Panet A, Linson E, Ivring C et al. (2006). Phase I/II trial of intravenous NDV-HUJ oncolytic virus in
recurrent glioblastoma multiforme. Molecular Therapy, 13(1): 221218. DOI: https://www.doi.org/10.1016/j.vmthe.2005.08.016
Garg T, Bhandari S, Rath G, and Goyal AK (2015). Current strategies for targeted delivery of bio-active drug molecules in the treatment of brain tumor. Journal of Drug Targeting, 23(10): 865-887. DOI: https://www.doi.org/10.3109/1061186X.2015.1029930
Garmaroudi GA Karimi F, Naeini LG, Kokabian P, and Givtaj N (2022). Therapeutic efficacy of oncolytic viruses in fighting cancer: Recent advances and perspective. Oxidative Medicine and Cellular Longevity, 2022: 3142306. DOI:
https://www.doi .org/10.115 5/2022/3142306
Getabalew M, Alemneh T, Akeberegn D, Getahun D, and Zewdie D (2019). Epidemiology, diagnosis and prevention of Newcastle disease in poultry. American Journal of Biomedicine Science and Research, 3(1): 50-59. DOI:
https://www.doi.org/10.34297/AJBSR.2019.03.000632
Ghasemi Darestani N, Gilmanova AI, Al-Gazally ME, Zekiy AO, Ansari MJ, Zabibah RS, Jawad MA, Al-Shalah SAJ, Rizaev JA, Alnassar YS et al. (2023). Mesenchymal stem cell-released oncolytic virus: An innovative strategy for cancer treatment. Cell Communication and Signaling, 21(1): 43. DOI:
https://www.doi.org/10.1186/s12964-022-01012-0
Ghorbankhani GA, Mohammadi A, Kazemipur N, Morovati S, Fard BG, and Habibabadi SN (2023). Apoptotic activity of Newcastle disease virus in comparison with nisin A in MDA-MB-231 cell line. Veterinary Research Forum, 14(1): 29-37. DOI: https://www.doi.org/10.30466/vrf.2022.542258.3297
Hajjafari A, Simab PA, Sadr S, Lotfalizadeh N, and Borji H (2022). Caenorhabditis elegans as a valuable model for studying apoptosis and autophagy in cancer development: Current insights, future directions, and challenges. Journal of Lab Animal Research, 1(1): 41-46. DOI: https://www.doi.org/10.58803/jlar.v1i1.12
Howells A, Marelli G, Lemoine NR, and Wang Y (2017). Oncolytic viruses—interaction of virus and tumor cells in the battle to eliminate cancer. Frontiers in Oncology, 7: 195. DOI: https://www.doi.org/10.3389/fonc.2017.00195
Hu H, Xia Q, Hu J, and Wang S (2022). Oncolytic viruses for the treatment of bladder cancer: Advances, challenges, and prospects. Journal of Clinical Medicine, 11(23): 6997. DOI:
https://www.doi.org/10.3390/jcm11236997
Hwang JK, Hong J, and Yun CO (2020). Oncolytic viruses and immune checkpoint inhibitors: Preclinical developments to clinical trials. International Journal of Molecular Sciences, 21(22): 8627. DOI: https://www.doi.org/10.3390/ijms21228627
Jafari M, Kadkhodazadeh M, Shapourabadi MB, Goradel NH, Shokrgozar MA, Arashkia A, Abdoli S, and Sharifzadeh Z (2022). Immunovirotherapy: The role of antibody based therapeutics combination with oncolytic viruses. Frontiers in Immunology, 13: 1012806. DOI: https://www.doi.org/10.3389/fimmu.2022.1012806
Jagtap RB, Raja A, Parthiban M, and Palanisamy M (2017). Dose and strain dependent induction of cell death of human breast cancer cells (mcf-7) by Newcastle disease virus. Journal of Animal Health Production, 5(1): 29-34. DOI:
http://www.doi.org/10.14737/journal.jahp/2017/5.1.29.34
Jiang K, Li Y, Zhu Q, Xu J, Wang Y, Deng W, Liu Q, Zhang G, and Meng S (2014). Pharmacological modulation of autophagy enhances Newcastle disease virus-mediated oncolysis in drug-resistant lung cancer cells. BMC Cancer, 14(1): 551. DOI: https://www.doi.org/10.1186/1471-2407-14-551
Kadhim ZA, Sulaiman GM, Al-Shammari AM, Khan RA, Al Rugaie O, and Mohammed HA (2022). Oncolytic Newcastle disease virus co-delivered with modified PLGA nanoparticles encapsulating temozolomide against glioblastoma cells: Developing an effective treatment strategy. Molecules, 27(18): 5757. DOI: https://www.doi.org/10.3390/molecules27185757
Kalafati E, Drakopoulou E, Anagnou NP, and Pappa KI (2023). Developing oncolytic viruses for the treatment of cervical cancer. Cells, 12(14): 1838. DOI: https://www.doi.org/10.3390/cells12141838
Kari S, Subramanian K, Altomonte IA, Murugesan A, Yli-Harja O, and Kandhavelu M (2022). Programmed cell death detection methods: A systematic review and a categorical comparison. Apoptosis, 27(7-8): 482-508. DOI: https://www.doi.org/10.1007/s10495-022-01735-
y
Karimi S, Pohl S, Scholer F, Cavedon L, and Zobel J (2010). Boolean versus ranked querying for biomedical systematic reviews. BMC Medical Informatics and Decision Making. 10(1): 58. DOI: https://www.doi.org/10.1186/1472-6947-10-58
Kaufman HL, Kohlhapp FJ, and Zloza A (2015). Oncolytic viruses: A new class of immunotherapy drugs. Nature reviews Drug Discovery, 14(9): 642-662. DOI: https://www.doi .org/10. 103 8/nrd4663
Koks CA, Garg AD, Ehrhardt M, Riva M, Vandenberk L, Boon L, Vleeschouwer SD, Agostinis P, Graf N, and Gool SWV (2015). Newcastle disease virotherapy induces long-term survival and tumor-specific immune memory in orthotopic glioma through the induction of immunogenic cell death. International Journal of Cancer, 136(5): E313-E325. DOI:
https://www.doi.org/10.1002/ijc.29202
Kontermann RE, Ungerechts G, and Nettelbeck DM (2021). Viro-antibody therapy: Engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics. MAbs, 13(1): 1982447. DOI: https://www.doi.org/10.1080/19420862.2021.1982447
Kooti W, Esmaeili Gouvarchin Ghaleh H, Farzanehpour M, Dorostkar R, Jalali Kondori B, and Bolandian M (2021). Oncolytic viruses and cancer, do you know the main mechanism?. Frontiers in Oncology, 11: 761015. DOI: https://www.doi.org/10.3389/fonc.2021.761015
Koppers-Lalic D and Hoeben RC (2011). Non-human viruses developed as therapeutic agent for use in humans. Reviews in Medical Virology, 21(4): 227-239. DOI: https://www.doi .org/10. 1002/rmv.694
Krabbe T and Altomonte J (2018). Fusogenic viruses in oncolytic immunotherapy. Cancers, 10(7): 216. DOI: https://www.doi.org/10.3390/cancers10070216
Lam HY, Yeap SK, Rasoli M, Omar AR, Yusoff K, Suraini AA, and Alitheen N (2011). Safety and clinical usage of Newcastle disease virus in cancer therapy. BioMed Research International, 2011: 718710. DOI: https://www.doi.org/10.1155/2011/718710
Laurie SA, Bell JC, Atkins HL, Roach J, Bamat MK, O'Neil JD, Roberts M, Groene WS, and Lorence RM (2006). A phase 1 clinical study of intravenous administration of PV701, an oncolytic virus, using two-step desensitization. Clinical Cancer Research, 12(8): 25552562. DOI: https://www.doi.org/10.1158/1078-0432.CCR-05-2038
Li X, Sun X, Wang B, Li Y, and Tong J (2022). Oncolytic virus-based hepatocellular carcinoma treatment: Current status, intravenous delivery strategies, and emerging combination therapeutic solutions. Asian Journal of Pharmaceutical Sciences, 18(1): 100771. DOI: https://www.doi.org/10.1016/j.ajps.2022.100771
Lin D, Shen Y, and Liang T (2023). Oncolytic virotherapy: Basic principles, recent advances and future directions. Signal Transduction and Targeted Therapy, 8(1): 156. DOI: https://www.doi.org/10.1038/s41392-023-01407-6
Liu H, Wang Z, Wu Y, Zheng D, Sun C, Bi D, Zuo Y, and Xu T (2007 a). Molecular epidemiological analysis of Newcastle disease virus isolated in China in 2005. Journal of Virological Methods, 140(1-2): 206-211. DOI: https://www.doi.org/10.1016/j.jviromet.2006.10.012
Liu TC, Galanis E, and Kirn D (2007 b). Clinical trial results with oncolytic virotherapy: A century of promise, a decade of progress. Nature Clinical Practice Oncology, 4(2): 101-117. DOI: https://www.doi .org/10.103 8/ncponc0736
Locy H, De Mey S, De Mey W, De Ridder M, Thielemans K, and Maenhout SK (2018). Immunomodulation of the tumor
microenvironment: Turn foe into friend. Frontiers in Immunology, 9: 2909. DOI: https://www.doi.org/10.3389/fimmu.2018.02909
Lorence RM, Scot Roberts M, O'Neil JD, Groene WS, Miller JA, Mueller SN, and Bamat M (2007). Phase 1 clinical experience using intravenous administration of PV701, an oncolytic Newcastle disease virus. Current Cancer Drug Targets, 7(2): 157-167. DOI: https://www.doi.org/10.2174/156800907780058853
Malogolovkin A, Gasanov N, Egorov A, Weener M, Ivanov R and Karabelsky A (2021). Combinatorial approaches for cancer treatment using oncolytic viruses: Projecting the perspectives through clinical trials outcomes. Viruses, 13(7): 1271. DOI: https://www.doi.org/10.3390/v13071271
Marchini A, Scott EM, and Rommelaere J (2016). Overcoming barriers in oncolytic virotherapy with HDAC inhibitors and immune checkpoint blockade. Viruses, 8(1): 9. DOI: https://www.doi.org/10.3390/v8010009
Mardi A, Shirokova AV, Mohammed RN, Keshavarz A, Zekiy AO, Thangavelu L, Muhammad TAM, Marofi F, Shomali N, Zamani A et al. (2022). Biological causes of immunogenic cancer cell death (ICD) and anti-tumor therapy; Combination of oncolytic virus-based immunotherapy and CAR T-cell therapy for ICD induction. Cancer Cell International, 22(1): 168. DOI: https://www.doi.org/10.1186/s12935-022-02585-z
Markman JL and Shiao SL (2015). Impact of the immune system and immunotherapy in colorectal cancer. Journal of Gastrointestinal Oncology, 6(2): 208-223. DOI: https://www.doi.org/10.3978/j.issn.2078-6891.2014.077
Matveeva OV, Guo ZS, Shabalina SA, and Chumakov PM (2015). Oncolysis by paramyxoviruses: Multiple mechanisms contribute to therapeutic efficiency. Molecular Therapy-Oncolytics, 2: MTO201511 DOI: https://www.doi.org/10.1038/mto.2015.11
Meng Q, He J, Zhong L, and Zhao Y (2021). Advances in the study of antitumour immunotherapy for Newcastle disease virus. International Journal of Medical Sciences, 18(11): 2294-2302. DOI: https://www.doi.org/10.7150/ijms.59185
Moehler M, Delic M, Goepfert K, Aust D, Grabsch HI, Halama N, Heirich B, Julie C, Lordick F, Lutz MP et al. (2016). Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives. European Journal of Cancer, 59: 160-170. DOI: https://www.doi.org/10.1016/j.ejca.2016.02.020
Mohammed MS, Al-Taee MF, and Al-Shammari AM (2019). Caspase dependent and independent anti-hematological malignancy activity of AMHA1 attenuated newcastle disease virus. International Journal of Molecular and Cellular Medicine, 8(3): 211-222. DOI: https://www.doi.org/10.22088/IJMCM.BUMS.8.3.211
Nakao S, Arai Y, Tasaki M, Yamashita M, Murakami R, Kawase T, Amino N, Nakatake M, Kurosaki H, Mori M et al. (2020). Intratumoral expression of IL-7 and IL-12 using an oncolytic virus increases systemic sensitivity to immune checkpoint blockade. Science Translational Medicine, 12(526): eaax7992. DOI: https://www.doi.org/10.1126/scitranslmed.aax7992
Nirmala JG and Lopus M (2020). Cell death mechanisms in eukaryotes. Cell Biology and Toxicology, 36: 145-164. DOI: https://www.doi.org/10.1007/s10565-019-09496-2
O'farrell A, Shnyder S, Marston G, Coletta P, and Gill J (2013). Non-invasive molecular imaging for preclinical cancer therapeutic development. British Journal of Pharmacology, 169(4): 719-735. DOI: https://www.doi.org/10.1111/bph.12155
Oladejo M, Paulishak W, and Wood L (2022). Synergistic potential of immune checkpoint inhibitors and therapeutic cancer vaccines. Seminars in Cancer Biology, 88: 81-95. DOI: https://www.doi.org/10.1016/j.semcancer.2022.12.003
Palanivelu L, Liu CH, and Lin LT (2023). Immunogenic cell death: The cornerstone of oncolytic viro-immunotherapy. Frontiers in
Immunology, 13: 1038226. DOI:
https://www.doi.org/10.3389/fimmu.2022.1038226
Pierce KM, Miklavcic WR, Cook KP, Hennen MS, Bayles KW, Hollingsworth MA, Brooks A, Pullan J, and Dailey K (2021). The evolution and future of targeted cancer therapy: From nanoparticles, oncolytic viruses, and oncolytic bacteria to the treatment of solid tumors. Nanomaterials, 11(11): 3018. DOI: https://www.doi.org/10.3390/nano11113018
Prestwich RJ, Harrington KJ, Pandha HS, Vile RG, Melcher AA, and Errington F (2008). Oncolytic viruses: A novel form of immunotherapy. Expert Review of Anti-cancer Therapy, 8(10): 1581-1588. DOI: https://www.doi.org/10.1586/14737140.8.10.1581
Raja J, Ludwig JM, Gettinger SN, Schalper KA, and Kim HS (2018). Oncolytic virus immunotherapy: Future prospects for oncology. Journal for Immunotherapy of Cancer, 6(1): 140. DOI: https://www.doi.org/10.1186/s40425-018-0458-z
Randall RE and Goodbourn S (2008). Interferons and viruses: An interplay between induction, signalling, antiviral responses and virus countermeasures. Journal of General Virology, 89(1): 1 -47. DOI: https://www.doi.org/10.1099/vir0.83391-0
Rezaei R, Esmaeili Gouvarchin Ghaleh H, Farzanehpour M, Dorostkar R, Ranjbar, Bolandian M, Nodooshan MM, and Alvanegh AG (2022). Combination therapy with CAR T cells and oncolytic viruses: A new era in cancer immunotherapy. Cancer Gene Therapy, 29(6): 647-660. DOI: https://www.doi.org/10.1038/s41417-021-00359-9
Ricca JM, Oseledchyk A, Walther T, Liu C, Mangarin L, Merghoub T, Wolchok JD, and Zamarin D (2018). Pre-existing immunity to oncolytic virus potentiates its immunotherapeutic efficacy. Molecular Therapy, 26(4): 1008-1019. DOI: https://www.doi.org/10.1016/] .ymthe.2018.01.019
Ripp J, Hentzen S, and Saeed A (2022). Oncolytic viruses as an adjunct to immune checkpoint inhibition. Frontiers in Bioscience-Landmark, 27(5): 151. DOI: https://www.doi.org/10.31083/j.fbl2705151
Rius-Rocabert S, García-Romero N, García A, Ayuso-Sacido A, and Nistal-Villan E (2020). Oncolytic virotherapy in glioma tumors. International Journal of Molecular Sciences, 21(20): 7604. DOI: https://www.doi.org/10.3390/ijms21207604
Rush BS, Djagbare MD, Speir JA, and Sanyal G (2020). Ionic strength-dependent, reversible pleomorphism of recombinant newcastle disease virus. Journal of Virology, 94(22): 725. DOI: https://www.doi.org/10.1128/JVI.01677-20
Russell SJ (2002). RNA viruses as virotherapy agents. Cancer Gene Therapy, 9(12): 961-966. DOI:
https://www.doi.org/10.1038/sj.cgt.7700535
Sadr S, Ghiassi S, Lotfalizadeh N, Simab PA, Hajjafari A, and Borji H (2023 a). Anti-tumor mechanisms of molecules secreted by Trypanosoma cruzi in colon and breast cancer: A review. AntiCancer Agents in Medicinal Chemistry, 23(15): 1710-1721. DOI: https://www.doi.org/10.2174/1871520623666230529141544
Sadr S, Simab PA, and Borji H (2023 b). CRISPR-Cas9 as a potential cancer therapy agent: An update. Research in Biotechnology and Environmental Science, 2(1): 12-17. DOI: https://www.doi.org/10.58803/RBES.2023.2.1.02
Sadr S, Yousefsani Z, Simab PA, Jafari Rahbar Alizadeh A, Lotfalizadeh N, and Borji H (2023 c). Trichinella spiralis as a potential antitumor agent: An update. World Veterinary Journal, 13(1): 65-74. DOI: https://www.doi.org/ 10.54203/scil.2023 .wvj 7
Sadri M, Najafi A, Rahimi A, Behranvand N, Kazemi MH, Khorramdelazad H, and Falak R (2023). Hypoxia effects on oncolytic virotherapy in Cancer: Friend or foe?. International Immunopharmacology, 122: 110470. DOI:
https://www.doi.org/ 10.1016/j .intimp.2023. 110470
Saeed M, Sadr S, Gharib A, Lotfalizadeh N, Hajjafari A, Simab PA, and Borji H (2022). Phytosomes: A promising nanocarrier for enhanced delivery of herbal compounds in cancer therapy. Journal of Lab
Animal Research, 1(1): 26-32. DOI:
https://www.doi.org/10.58803/jlar.v1i1.8
Samal SK (2021). Paramyxoviruses as vaccine vectors. In: T. Vanniasinkam, S. K. Tikoo, S. K. Samal, (Editors), Viral vectors in veterinary vaccine development. Springer Cham, pp. 113-139. DOI: https://www.doi.org/10.1007/978-3-030-51927-8 8
Sánchez D, Pelayo R, Medina LA, Vadillo E, Sánchez R, Núñez L, Maus G, and Silva RES (2015). Newcastle disease virus: Potential therapeutic application for human and canine lymphoma. Viruses, 8(1): 3. DOI: https://www.doi.org/10.3390/v8010003
Sasso E, D'Alise AM, Zambrano N, Scarselli E, Folgori A, and Nicosia A (2020). New viral vectors for infectious diseases and cancer. Seminars in Immunology, 50: 101430. DOI: https://www.doi.org/10.1016/j.smim.2020.101430
Schirrmacher V (2020). Cancer vaccines and oncolytic viruses exert profoundly lower side effects in cancer patients than other systemic therapies: A comparative analysis. Biomedicines, 8(3): 61. DOI: https://www.doi.org/10.3390/biomedicines8030061
Schirrmacher V (2022 a). Molecular mechanisms of anti-neoplastic and immune stimulatory properties of oncolytic Newcastle disease virus. Biomedicines, 10(3): 562. DOI:
https://www.doi.org/10.3390/biomedicines10030562
Schirrmacher V, van Gool S, and Stuecker W (2022 b). Counteracting immunosuppression in the tumor microenvironment by oncolytic Newcastle disease virus and cellular immunotherapy. International Journal of Molecular Sciences, 23(21): 13050. DOI: https://www.doi.org/10.3390/ijms232113050
Scott EM, Duffy MR, Freedman JD, Fisher KD, and Seymour LW (2018). Solid tumor immunotherapy with T cell engager-armed oncolytic viruses. Macromolecular Bioscience, 18(1): 1700187. DOI: https://www.doi.org/10.1002/mabi.201700187
Shao X, Wang X, Guo X, Jiang K, Ye T, Chen J, Fang J, Gu L, Wang S, Zhang G et al. (2019). STAT3 contributes to oncolytic newcastle disease virus-induced immunogenic cell death in melanoma cells. Frontiers in Oncology, 9: 436. DOI: https://www.doi.org/10.3389/fonc.2019.00436
Shaver KA, Croom-Perez TJ, and Copik AJ (2021). Natural killer cells: The linchpin for successful cancer immunotherapy. Frontiers in Immunology, 12: 679117. DOI:
https://www.doi.org/10.3389/fimmu.2021.679117
Siafaka P and Gündogdu EA (2023). New Era on combining both imaging and drug delivery to treat cancer. Current Pharmaceutical Biotechnology, 24(7): 832-855. DOI:
https://www.doi.org/10.2174/1389201023666220617152334
Song H, Zhong LP, He J, Huang Y, and Zhao Y-X (2019). Application of Newcastle disease virus in the treatment of colorectal cancer. World Journal of Clinical Cases, 7(16): 21-43. DOI: https://www.doi.org/10.12998/wjcc.v7.i16.2143
Suarez DL, Miller PJ, Koch G, Mundt E, and Rautenschlein S (2020). Newcastle disease, other avian paramyxoviruses, and avian metapneumovirus infections. In: D. E. Swayne, M. Boulianne, C. M. Logue, L. R. McDougald, V. Nair, D. L. Suarez, S. de Wit, T. Grimes, Johnson D, Kromm M et al. (Editors). Diseases of Poultry, 14th Edition. Wiley, pp. 109-166. DOI: https://www.doi.org/10.1002/9781119371199.ch3
Svensson-Arvelund J, Cuadrado-Castano S, Pantsulaia G, Kim K, Aleynick M, Hammerich L, Yellin M, Marsh H, Oreper D et al. (2022). Expanding cross-presenting dendritic cells enhances oncolytic virotherapy and is critical for long-term anti-tumor immunity. Nature Communications, 13(1): 7149. DOI: https://www.doi.org/10.1038/s41467-022-34791-8
Taguchi S, Fukuhara H, Homma Y, and Todo T (2017). Current status of clinical trials assessing oncolytic virus therapy for urological cancers. International Journal of Urology, 24(5): 342-351. DOI: https://www.doi.org/10.1111/iju.13325
Tang C, Li L, Mo T, Na J, Qian Z, Fan D, Sun X, Yao M, PanH L, uang Y et al. (2022). Oncolytic viral vectors in the era of diversified cancer therapy: From preclinical to clinical. Clinical and Translational Oncology, 24(9): 1682-1701. DOI:
https://www.doi.org/ 10.1007/s12094-022-02830-x
Tian Y, Xie D, and Yang L (2022). Engineering strategies to enhance oncolytic viruses in cancer immunotherapy. Signal Transduction and Targeted Therapy, 7(1): 117. DOI: https://www.doi.org/10.1038/s41392-022-00951-x
Tornesello AL, Tagliamonte M, Buonaguro FM, Tornesello ML, and Buonaguro L (2022). Virus-like particles as preventive and therapeutic cancer vaccines. Vaccines, 10(2): 227. DOI: https://www.doi.org/10.3390/vaccines10020227
Turnis ME, Andrews LP, and Vignali DA (2015). Inhibitory receptors as targets for cancer immunotherapy. European Journal of Immunology, 45(7): 1892-1905. DOI:
https://www.doi.org/10.1002/eji.201344413
Twumasi-Boateng K, Pettigrew JL, Kwok YE, Bell JC, and Nelson BH
(2018). Oncolytic viruses as engineering platforms for combination immunotherapy. Nature Reviews Cancer, 18(7): 419-432. DOI: https://www.doi.org/10.1038/s41568-018-0009-4
Ul-Rahman A, Ishaq HM, Raza MA, and Shabbir MZ (2022). Zoonotic potential of Newcastle disease virus: Old and novel perspectives related to public health. Reviews in Medical Virology, 32(1): e2246. DOI: https://www.doi.org/10.1002/rmv.2246
Vijayakumar G, McCroskery S, and Palese P (2020). Engineering Newcastle disease virus as an oncolytic vector for intratumoral delivery of immune checkpoint inhibitors and immunocytokines. Journal of Virology, 94(3): e01677-19. DOI: https://www.doi.org/10.1128/JVI.01677-19
Vile R, Ando D, and Kirn D (2002). The oncolytic virotherapy treatment platform for cancer: Unique biological and biosafety points to consider. Cancer Gene Therapy, 9(12): 1062-1067. DOI: https://www.doi.org/10.1038/sj.cgt.7700548
Wang Y, Wang M, Wu HX, and Xu RH (2021). Advancing to the era of cancer immunotherapy. Cancer Communications, 41(9): 803-829. DOI: https://www.doi.org/10.1002/cac2.12178
Wollmann G, Ozduman K, and Van Den Pol AN (2012). Oncolytic virus therapy of glioblastoma multiforme-concepts and candidates. Cancer Journal, 18(1): 69-81. DOI:
https://www.doi.org/10.1097/PPO.0b013e31824671c9
Yaghoubi N, Soltani A, Ghazvini K, Hassanian SM, and Hashemy SI
(2019). PD-1/PD-L1 blockade as a novel treatment for colorectal cancer. Biomedicine & Pharmacotherapy, 110: 312-318. DOI: https://www.doi.org/10.1016/j .biopha.2018.11.105
Yang C, Hua N, Xie S, Wu Y, Zhu L, Wang S, and Tang X (2021). Oncolytic viruses as a promising therapeutic strategy for hematological malignancies. Biomedicine & Pharmacotherapy, 139: 111573. DOI: https://www.doi.org/10.1016/j.biopha.2021.111573
Yu R, Zhu B, and Chen D (2022). Type I interferon-mediated tumor immunity and its role in immunotherapy. Cellular and Molecular Life Sciences, 79(3): 191 . DOI:
https://www.doi .org/10. 1007/s00018-022-04219-z
Yurchenko KS, Zhou P, Kovner AV, Zavjalov EL, Shestopalova LV, and Shestopalov AM (2018). Oncolytic effect of wild-type Newcastle disease virus isolates in cancer cell lines in vitro and in vivo on xenograft model. PLoS One, 13(4): e0195425. DOI: https://www.doi.org/10.1371/journal.pone.0195425
Zamarin D, Holmgaard RB, Subudhi SK, Park JS, Mansour M, Palese P, Merghoub T, Wolchok J, and Allison J (2014). Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Science Translational Medicine, 6(226): 226-232. DOI:
https://www.doi.org/10.1126/scitranslmed.3008095
Zamarin D and Palese P (2012). Oncolytic Newcastle disease virus for cancer therapy: Old challenges and new directions. Future Microbiology, 7(3): 347-367. DOI: https://www.doi.org/10.2217/fmb.12.4
Zeng J, Li X, Sander M, Zhang H, Yan G, and Lin Y (2021). Oncolytic viro-immunotherapy: An emerging option in the treatment of gliomas. Frontiers in Immunology, 12: 721830. DOI: https://www.doi.org/10.3389/fimmu.2021.721830
Zhang B and Cheng P (2020). Improving anti-tumor efficacy via combinatorial regimens of oncolytic virotherapy. Molecular Cancer, 19(1): 158. DOI: https://www.doi.org/10.1186/s12943-020-01275-6
Zhao B, Wu J, Li H, Wang Y, Wang Y, Xing H, Wang Y, and Ma W (2023). Recent advances and future challenges of tumor vaccination therapy for recurrent glioblastoma. Cell Communication and Signaling, 21(1): 74. DOI: https://www.doi.org/10.1186/s12964-023-01098-0
Zhao L and Liu H (2012). Newcastle disease virus: A promising agent for tumour immunotherapy. Clinical and Experimental Pharmacology and Physiology, 39(8): 725-730. DOI:
https://www.doi.org/10.1111/j.1440-1681.2011.05662.x
Zheng M, Huang J, Tong A, and Yang H (2019). Oncolytic viruses for cancer therapy: barriers and recent advances. Molecular Therapy-Oncolytics, 15: 234-47. DOI: https://www.doi.org/10.1016/j.omto.2019.10.007
Zhu S, Zhang T, Zheng L, Liu H, Song W, Liu D, Li Z, and Pan C (2021). Combination strategies to maximize the benefits of cancer immunotherapy. Journal of Hematology & Oncology, 14(1): 156. DOI: https://www.doi.org/10.1186/s13045-021-01164-5
Publisher's note: Scienceline Publication Ltd. remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
[/£> 0 I Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2023
