Abstract
Oncolytic viruses (OVs) infect, multiply, and finally remove tumor cells selectively, causing no damage to normal cells in the process. Because of their specific features, such as, the ability to induce immunogenic cell death and to contain curative transgenes in their genomes, OVs have attracted attention as candidates to be utilized in cooperation with immunotherapies for cancer treatment. This treatment takes advantage of most tumor cells' inherent tendency to be infected by certain OVs and both innate and adaptive immune responses are elicited by OV infection and oncolysis. OVs can also modulate tumor microenvironment and boost anti-tumor immune responses. Mesenchymal stem cells (MSC) are gathering interest as promising anti-cancer treatments with the ability to address a wide range of cancers. MSCs exhibit tumor-trophic migration characteristics, allowing them to be used as delivery vehicles for successful, targeted treatment of isolated tumors and metastatic malignancies. Preclinical and clinical research were reviewed in this study to discuss using MSC-released OVs as a novel method for the treatment of cancer.
Video Abstract
Similar content being viewed by others
Introduction
In recent years, early diagnosis of some cancer types, along with the development of cancer-specific treatments, has led to an increase in cancer patients' survival rates [1]. However, the short half-life of several cancer-specific medications, restricted distribution to particular tumor types, and negative impacts on healthy tissues are important barriers to treatment. Actually, the primary goal of cancer treatment is to develop anticancer medications that effectively target malignant cells while preserving healthy tissue [2, 3]. A few instances of metastatic cancer have been effectively treated using traditional methods [4]. As a result, develo** a novel therapeutic approach to inhibit metastasis is crucial, especially given the issues with current cancer treatment strategies, such as drug resistance and systemic side effects [5, 6].
Beyond the capacity of some viruses to mediate oncogenesis and their use in the development of immunotherapies, such as the cytomegalovirus (CMV) gliomagenesis and its implications in the development of CMV-specific adoptive T cell immunotherapies, viruses themselves can be used as therapeutic agents to target tumor cells [7]. In this way, oncolytic viruses (OVs) are defined as naturally occurring or genetically manipulated viruses that exclusively replicate and grow in tumor cells and kill them while sparing normal cells [8, 9]. Oncolytic viral therapy is a new strategy of cancer therapy that has shown promise in preclinical and clinical trials [10, 11]. Altered mutants of human viruses, wild-type animal viruses that are cytotoxic to human cancer cells, and live virus vaccines are among the viruses used in this therapy. Adenovirus, measles virus, reovirus, herpes simplex virus, vesicular stomatitis, Newcastle disease virus, vaccinia virus, and poliovirus are some of these viruses [12, 13]. OVs have the ability to directly lyse cancer cells but this is not the sole advantage of them; it is now well acknowledged that one of the most essential aspects of virotherapy is the cytotoxic immune response they can trigger or reactivate in patients, which results in therapeutic responses [14, 15] and was shown in glioblastoma, B cell malignancy, metastatic melanoma, and liver cancer [16,17,18,19,20]. Indeed, multiple investigators have reported on the possible use of OVs for cancer treatment, with a demonstration of long-term prognosis [21]. A variety of factors, including viral elimination by the immune system and viral uptake by tissues and organs, can influence viral effectiveness in reaching cancerous tissues [22, 23, 24]. To boost treatment efficacy, effective carrier vehicles are essential for delivering OVs to tumor sites. Adult stem or progenitor cells have been extracted from a variety of tissues, including the brain, heart, and kidney, and have shown promise in treating a variety of diseases [25,26,27]. In both in vitro and many murine cancer models, unmodified MSC has been demonstrated to have anti-tumor activities. This is due to antitumor substances generated by MSCs, which limit the growth of cancer cells including glioma, melanoma, lung cancer, hepatoma, and breast cancer [28,29,30,31,32,33]. Furthermore, MSCs have been utilized as carriers because of their known tumor-specific homing ability, which allows for the virus's safe transportation and releases on the tumor site [34,268, 269]. In spite of the route of injection of MSCs [270].
Furthermore, biological targeting techniques have been developed to satisfy the demand for greater target stringency following systemic administration of MSCs, particularly when the disease to be treated is extensive, as in metastases [271, 272]. It includes evidence-based techniques aiming at enhancing MSC homing, binding selectivity to a target tissue, and persistence within the target environment [262]. Indeed, to regulate MSC homing potential, various approaches have been established, including altering the MSC culture conditions to promote the production of homing-related compounds, redesigning the cell membrane to increase homing, and adjusting the target tissue to better attract MSCs [273].
OV penetration
Epithelial junctions function as an obstacle to the intracellular infiltration of OVs, particularly adenoviruses, in carcinomas [274]. Indeed, phenotype changes during metastasis, including EMT and later mesenchymal-to-epithelial transitions (MET), which tighten epithelial connections and make therapy challenging [275, 276]. Yumul et al. created epithelial junction openers (JO) by modifying Ad5Δ24. They found that oncolytic Ads that express JO had a substantially higher anti-tumor activity than unmodified viruses [274]. Moreover, the extracellular matrix (ECM) and cellular connections are significant barriers that are related to the spread and penetration of OVs. In fact, OVs must cross the complex ECM to reach tumor cells and lysis them [277]. Pre-treatment of cancer with collagenase [278] or co-administration of hyaluronidase with oncolytic adenoviruses [279] resulted in increased viral dissemination. Additionally, altering OVs to express matrix metalloproteinases-1 and -8 causes cancer-associated sulfated glycosaminoglycans to be degraded, resulting in improved viral dispersion and treatment efficiency [280]. Tumor cell apoptosis also promotes viral dissemination. For instance, Nagano et al. found that cytotoxic substances induced apoptosis and activated caspase-8, resulting in greater intratumoral uptake and anti-cancer effect of oncolytic HSV. They hypothesized that reducing or eliminating apoptotic tumor cells resulted in channel-like structures and empty areas, enabling oncolytic HSV to disseminate more easily [281].
Hypoxic effect
Hypoxia is a characteristic of solid tumors that emerges throughout the formation and development of the tumor and has been demonstrated to have paradoxical impacts on OVs [282]. Hypoxic circumstances have been observed to decrease viral proliferation and lytic capacity without changing the expression of surface receptors [283, 284]. Because hypoxia may cause cell cycle arrest, this feature might influence the capability of oADs and other viruses that rely on cell cycle advancement to reproduce [284]. Clarke et al. created an oncolytic adenovirus in which the expression of the E1A gene is regulated by the hypoxia-response factor-containing promoter to counteract hypoxic suppression of viral reproduction and to get the benefits of hypoxic conditions for homing [285]. However, in 2009, two groups revealed that a hypoxic condition increases oncolytic HSV viral proliferation [286, 287]. This might be due to HSV's intrinsic affinity to low-oxygen cells or DNA damage caused by oxygen-derived free radicals, which promotes HSV reproduction [286].
Treatment durability
Tumors frequently recur after great initial treatment results. Stem cell treatment using a single substance, like other chemotherapies, isn't always successful in removing tumors [288, 289]. As a result, a reasonable medication combination should be determined [290]. Many different combination therapies have been tried to see whether they can help with treatment persistence. For instance, irradiating cancer cells leads them to release molecules that promote MSC penetration across integral basement membranes, resulting in an increase in the amount of MSCs in cancers [291].
Modification
In addition to their inherent potential to lyse cancer cells, OVs can be modified to improve their lytic activity. For example, adenoviruses expressing the herpes simplex virus-1 thymidine kinase (HSV-1 TK) under the osteocalcin promoter have been designed to target bone cancers. HSV-1 TK could convert thymidine analogs, such as ganciclovir into monophosphates, which stop DNA synthesis and trigger cell death By incorporating into the DNA of reproducing cells [292, 293, 294]. OVs have been modified to improve immune responses even further. Most transgenes are designed to induce an adaptive immune response against cancer antigens or to contribute to the treatment of immune cell-depleted malignancies. Including, cytokines, chemokines, inhibitory receptors, co-stimulatory receptors, bispecific cell engagers, immunological ligands, and combinations of any of these [133, 295, 296]. For instance, researchers have engineered oncolytic viruses which can express IL-2, IL-12, IL-15, IL-6, IL-21, IL-18, IL-24, and granulocyte–macrophage colony-stimulating factor (GM-CSF) and activate various aspects of the immune system [295, 296]. Moreover, the immunosuppressive TME might be altered by inserting an immune stimulatory chemical into OV genomes. The most often utilized example is GM-CSF, which has been inserted into OV genomes as an immune stimulatory molecule to promote the maturation and recruitment of APCs, particularly DCs, as well as the recruitment of tumor antigen-specific T cells and NK cells [109]. On the other hand, one aspect of transgenic-armed OVs is that immune activation can be delayed depending on the viral promoter that regulates the transgene or by controlling protein translation. To avoid an overly-rapid immune response, the expression of transgenes should be postponed until the viral oncolysis is at its maximum [297]. Additionally, the kind of transgenic and the number of transgenes that may be included in a single viral construct are both influenced by the type of virus. Unlike DNA viruses, which can handle more transgenes without harming replication, RNA viruses generally have a shorter genome and can only encode a restricted number of them [133]. Furthermore, a modified oncolytic adenovirus expressing the TRAIL gene was recently utilized to treat a mouse model of pancreatic ductal adenocarcinoma (PDAC), a malignant and lethal malignancy with a poor prognosis and few treatment options. The study revealed that in a PDAC animal model, AD-MSCs carrying TRAIL specifically homed to the cancer site and significantly slowed tumor growth, with no toxicity or adverse effects [178].
MSCs can be also genetically manipulated or preconditioned to increase their intrinsic features, such as improved migration, adhesion, and survival, as well as reduced premature aging. For example, to improve MSC migration, CXCR1, 4, and 7 were overexpressed which CXCR1 binds to IL-8 and CXCR4 and CXCR7 bind to SDF-1. Also for increasing MSC adhesion ability, MSCs were genetically engineered to express higher levels of integrin-linked kinase (ILK) [298].
Conclusion and prospect
MSCs improve the anticancer efficacy of virotherapy in a variety of ways. Indeed, MSCs act as a reproduction site for OVs, allowing for the generation of more virions, which is advantageous for virotherapy. In addition, MSCs' tumor tropism and immunosuppressive activity enable the virus to specifically target the cancer site, increasing viral spread, and survival. MSCs, on the other hand, generate cytokines that attract immune cells to the TME, increasing the anticancer immune response. Moreover, oncolysis triggers the production of danger signal including TAAs and DAMPs/PAMPs, which stimulate local anticancer immune responses and alter the TME from immunosuppressive to immunostimulatory [45, 51].
Integrating MSCs with more effective OVs is a reasonable move towards enhancing therapeutic outcomes. Currently, there are four ongoing clinical trials using the OV-loaded MSCs for cancer therapy, which offer up a wide range of combinations with MSCs [299].
Altogether, further development of MSCs-OVs therapies may rely on a multifaceted strategy to select design parameters to improve the safety profile and efficacy of carrier cells, improve viral replication in MSCs, and establish patient eligibility criteria. For overcoming these obstacles some efforts have performed. For example, by manipulating the MSCs, it is feasible to enhance the clinical result. Polymers or other viral capsids might potentially be used to improve infectivity and viral replication [300, 301]. Also to control the adenovirus’s replication within MSCs, an all-in-one Tet-on system has been developed, which could help future studies to reach the optimum therapeutic effect of the oncolytic virus [183].
To summarize, although existing clinical trials will help to clarify the therapeutic efficacy of MSCs as OV cell carriers, further efforts should be undertaken to translate current viral and cellular preclinical achievements to the clinic, either as monotherapy or in combination with radiation, chemotherapy, or even immunotherapies.
Availability of data and materials
Not applicable.
Abbreviations
- OVs:
-
Oncolytic viruses
- TME:
-
Tumor microenvironment
- MSCs:
-
Mesenchymal stem cells
- UC-MSC:
-
Umbilical cord derived MSCs
- hMSCs:
-
Human MSCs
- BM-MSCs:
-
Bone marrow MSCs
- DAMPs:
-
Damage-associated molecular patterns
- PAMPs:
-
Pathogen-associated molecular patterns
- oAds:
-
Oncolytic adenovirus
- CRAds:
-
Conditional replication oncolytic adenoviruses
- oHSV:
-
Herpes simplex virus
- oMV:
-
Oncolytic measles virus
- EMT:
-
Epithelial-mesenchymal transition
- MET:
-
Mesenchymal-epithelial transitions
References
Amri A, Soltanian AR, Borzouei S. Survival rates and prognostic factors of thyroid cancer: a retrospective cohort study. J Parathyr Dis. 2022;10: e11162.
Stuckey DW, Shah K. Stem cell-based therapies for cancer treatment: Separating hope from hype. Nat Rev Cancer. 2014;14(10):683–91.
Engel J, Lategahn J, Rauh D. Hope and disappointment: covalent inhibitors to overcome drug resistance in non-small cell lung cancer. ACS Med Chem Lett. 2016;7:2–5.
Jamali S, et al. Strategy for treating the gastric cancer: a systematic review and meta-analysis. Int J Sci Res Dent Med Sci. 2020;2(1):6–11.
Ardalan M. Parathyroid carcinoma; an updated mini-review on current trends. J Parathyr Dis. 2016;4(2):57–9.
Roayaei M, Andalib Z, Akhavan A. The effect of oral zinc sulfate on prevention of chemotherapy induced oral mucositis in breast cancer patients treated with adriamycin and cyclophosphamide; a double-blind randomized clinical trial. J Nephropharmacol. 2023;12(1):e10533.
Daei Sorkhabi A, et al. The basis and advances in clinical application of cytomegalovirus-specific cytotoxic T cell immunotherapy for glioblastoma multiforme. Front Oncol. 2022;12:818447.
Aghi M, Martuza RL. Oncolytic viral therapies–the clinical experience. Oncogene. 2005;24(52):7802–16.
Parato KA, et al. Recent progress in the battle between oncolytic viruses and tumours. Nat Rev Cancer. 2005;5(12):965–76.
Liu T-C, Galanis E, Kirn D. Clinical trial results with oncolytic virotherapy: a century of promise, a decade of progress. Nat Clin Pract Oncol. 2007;4(2):101–17.
Lawler SE, Chiocca EA. Oncolytic virus-mediated immunotherapy: a combinatorial approach for cancer treatment. J Clin Oncol. 2015;33(25):2812–4.
Romero D. Oncolytic viruses prime antitumour immunity. Nat Rev Clin Oncol. 2018;15(3):135–135.
Engeland CE, Bell JC. Introduction to oncolytic virotherapy. Oncolytic Viruses. 2020. https://doi.org/10.1007/978-1-4939-9794-7_1.
Lichty BD, et al. Going viral with cancer immunotherapy. Nat Rev Cancer. 2014;14(8):559–67.
Scott EM, et al. Solid tumor immunotherapy with T cell engager-armed oncolytic viruses. Macromol Biosci. 2018;18(1):1700187.
Andtbacka RH, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(25):2780–8.
Markert JM, et al. Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. Mol Ther. 2009;17(1):199–207.
Cripe TP, et al. Phase 1 study of intratumoral Pexa-Vec (JX-594), an oncolytic and immunotherapeutic vaccinia virus, in pediatric cancer patients. Mol Ther. 2015;23(3):602–8.
Heo J, et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat Med. 2013;19(3):329–36.
Russell SJ, et al. Remission of disseminated cancer after systemic oncolytic virotherapy. Mayo Clin Proc. 2014;89(7):926–33.
Elankumaran S, et al. Type I interferon-sensitive recombinant newcastle disease virus for oncolytic virotherapy. J Virol. 2010;84(8):3835–44.
Roy DG, Bell JC, Bourgeois-Daigneault M-C. Magnetic targeting of oncolytic VSV-based therapies improves infection of tumor cells in the presence of virus-specific neutralizing antibodies in vitro. Biochem Biophys Res Commun. 2020;526(3):641–6.
Schirrmacher V, van Gool S, Stuecker W. Breaking therapy resistance: An update on oncolytic Newcastle disease virus for improvements of cancer therapy. Biomedicines. 2019;7(3):66.
Howells A, et al. Oncolytic viruses—interaction of virus and tumor cells in the battle to eliminate cancer. Front Oncol. 2017;7:195.
Corsten MF, Shah K. Therapeutic stem-cells for cancer treatment: hopes and hurdles in tactical warfare. Lancet Oncol. 2008;9(4):376–84.
Teo AK, Vallier L. Emerging use of stem cells in regenerative medicine. Biochem J. 2010;428(1):11–23.
Seif F, Kheirollah A, Babaahmadi-Rezaei H. Efficient isolation and identification of primary endothelial cells from bovine aorta by collagenase P. Immunopathol Persa. 2020;6(2):e15.
Maestroni G, Hertens E, Galli P. Factor (s) from nonmacrophage bone marrow stromal cells inhibit Lewis lung carcinoma and B16 melanoma growth in mice. Cell Mol Life Sci CMLS. 1999;55(4):663–7.
Nakamura K, et al. Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model. Gene Ther. 2004;11(14):1155–64.
Qiao C, et al. Human mesenchymal stem cells isolated from the umbilical cord. Cell Biol Int. 2008;32(1):8–15.
Qiao L, et al. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res. 2008;18(4):500–7.
Ahn J-O, et al. Human adipose tissue-derived mesenchymal stem cells inhibit melanoma growth in vitro and in vivo. Anticancer Res. 2015;35(1):159–68.
He N, et al. MSCs inhibit tumor progression and enhance radiosensitivity of breast cancer cells by down-regulating Stat3 signaling pathway. Cell Death Dis. 2018;9(10):1026.
Willmon C, et al. Cell carriers for oncolytic viruses: Fed Ex for cancer therapy. Mol Ther. 2009;17(10):1667–76.
**a X, et al. Mesenchymal stem cells as carriers and amplifiers in CRAd delivery to tumors. Mol Cancer. 2011;10(1):134.
Beckermann B, et al. VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer. 2008;99(4):622–31.
Kallifatidis G, et al. Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer. Cancer Gene Ther. 2008;15(4):231–40.
Ruano D, et al. First-in-human, first-in-child trial of autologous MSCs carrying the oncolytic virus Icovir-5 in patients with advanced tumors. Mol Ther. 2020;28(4):1033–42.
Tang Y, et al. In vivo tracking of neural progenitor cell migration to glioblastomas. Hum Gene Ther. 2003;14(13):1247–54.
Aboody KS, et al. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci. 2000;97(23):12846–51.
Shah K, et al. Glioma therapy and real-time imaging of neural precursor cell migration and tumor regression. Ann Neurol Off J Am Neurol Assoc Child Neurol Soc. 2005;57(1):34–41.
Sasportas LS, et al. Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci. 2009;106(12):4822–7.
Shah K. Mesenchymal stem cells engineered for cancer therapy. Adv Drug Deliv Rev. 2012;64(8):739–48.
Banijamali RS, et al. Kinetics of oncolytic reovirus T3D replication and growth pattern in mesenchymal stem cells. Cell J (Yakhteh). 2020;22(3):283.
Keshavarz M, et al. Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment. Virol J. 2020;17(1):64.
Hai C, et al. Application of mesenchymal stem cells as a vehicle to deliver replication-competent adenovirus for treating malignant glioma. Chin J Cancer. 2012;31(5):233.
Kazimirsky G, et al. Mesenchymal stem cells enhance the oncolytic effect of Newcastle disease virus in glioma cells and glioma stem cells via the secretion of TRAIL. Stem Cell Res Ther. 2016;7(1):149.
Melen GJ, et al. Influence of carrier cells on the clinical outcome of children with neuroblastoma treated with high dose of oncolytic adenovirus delivered in mesenchymal stem cells. Cancer Lett. 2016;371(2):161–70.
Leoni V, et al. Systemic delivery of HER2-retargeted oncolytic-HSV by mesenchymal stromal cells protects from lung and brain metastases. Oncotarget. 2015;6(33):34774.
Hoyos V, et al. Mesenchymal stromal cells for linked delivery of oncolytic and apoptotic adenoviruses to non-small-cell lung cancers. Mol Ther. 2015;23(9):1497–506.
Franco-Luzón L, et al. Systemic oncolytic adenovirus delivered in mesenchymal carrier cells modulate tumor infiltrating immune cells and tumor microenvironment in mice with neuroblastoma. Oncotarget. 2020;11(4):347–61.
Gimenez-Sanchez A, et al. Cellular Virotherapy increases tumor-infiltrating lymphocytes (TIL) and decreases their PD-1+ subsets in mouse immunocompetent models. Cancers. 2020;12(7):1920.
Mader EK, et al. Mesenchymal stem cell carriers protect oncolytic measles viruses from antibody neutralization in an orthotopic ovarian cancer therapy model. Clin Cancer Res. 2009;15(23):7246–55.
Hakkarainen T, et al. Human mesenchymal stem cells lack tumor tropism but enhance the antitumor activity of oncolytic adenoviruses in orthotopic lung and breast tumors. Hum Gene Ther. 2007;18(7):627–41.
Collet G, et al. Trojan horse at cellular level for tumor gene therapies. Gene. 2013;525(2):208–16.
Ferguson SD, et al. Crossing the boundaries: stem cells and gene therapy. Discov Med. 2010;9(46):192.
Salmasi Z, et al. Mesenchymal stem cells engineered by modified polyethylenimine polymer for targeted cancer gene therapy, in vitro and in vivo. Biotechnol Prog. 2020;36(6): e3025.
Momin EN, et al. The oncogenic potential of mesenchymal stem cells in the treatment of cancer: directions for future research. Curr Immunol Rev. 2010;6(2):137–48.
Yoon A-R, et al. Mesenchymal stem cell–mediated delivery of an oncolytic adenovirus enhances antitumor efficacy in hepatocellular carcinoma. Cancer Res. 2019;79(17):4503–14.
Rattigan Y, et al. Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu. Exp Cell Res. 2010;316(20):3417–24.
Ringe J, et al. Towards in situ tissue repair: human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2. J Cell Biochem. 2007;101(1):135–46.
Kidd S, et al. Origins of the tumor microenvironment: Quantitative assessment of adipose-derived and bone marrow–derived stroma. PLoS ONE. 2012;7(2): e30563.
Briko A, Kapravchuk V, Kobelev A, Hammoud A, Leonhardt S, Ngo C, Gulyaev Y, Shchukin, S. A way of bionic control based on EI, EMG, and FMG signals. Sensors (Basel, Switzerland) 2021;22(1):152. https://doi.org/10.3390/s22010152.
Briko A, Kapravchuk V, Kobelev A, Tikhomirov A, Hammoud A, Al-Harosh M, Leonhardt S, Ngo C, Gulyaev Y, Shchukin S. Determination of the geometric parameters of electrode systems for electrical impedance myography: a preliminary study. Sensors (Basel, Switzerland) 2021;22(1):97. https://doi.org/10.3390/s22010097.
Rustad KC, Gurtner GC. Mesenchymal stem cells home to sites of injury and inflammation. Adv Wound Care. 2012;1(4):147–52.
**e C, et al. Systemically infused mesenchymal stem cells show different homing profiles in healthy and tumor mouse models. Stem Cells Transl Med. 2017;6(4):1120–31.
Ma F, et al. Human umbilical cord mesenchymal stem cells promote breast cancer metastasis by interleukin-8-and interleukin-6-dependent induction of CD44+/CD24-cells. Cell Transplant. 2015;24(12):2585–99.
Smith CL, et al. Pre-exposure of human adipose mesenchymal stem cells to soluble factors enhances their homing to brain cancer. Stem Cells Transl Med. 2015;4(3):239–51.
Khalili M, et al. Evaluation of the survival rate and clinical outcome of nanodrug administration for the treatment of lung cancer: a systematic review and meta-analysis. Int J Sci Res Dent Med Sci. 2022;4(3):140–7.
Yoon A, et al. Mesenchymal stem cell–mediated delivery of an oncolytic adenovirus enhances antitumor efficacy in hepatocellular carcinomasystemic delivery of oncolytic adenovirus with MSC. Cancer Res. 2019;79(17):4503–14.
Dadras F, Sheikh V, Khoshjou F. Epithelial and endothelial mesenchymal transition and their role in diabetic kidney disease. J Renal Inj Prev. 2017;7(1):1–6.
Gao F, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. 2016;7(1):e2062–e2062.
Khare D, et al. Mesenchymal stromal cell-derived exosomes affect mRNA expression and function of B-lymphocytes. Front Immunol. 2018;9:3053.
Corcione A, et al. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107(1):367–72.
Palaniappan S, et al. Effect of Lung Specific Yoga Mudras on Pulmonary Function Tests in subjects with FEV1% predicted values less than 80%. Int J Sci Res Dent Med Sci. 2021;3(3):117–21.
Rozenberg A, et al. Human mesenchymal stem cells impact Th17 and Th1 responses through a prostaglandin E2 and myeloid-dependent mechanism. Stem Cells Transl Med. 2016;5(11):1506–14.
Spaggiari GM, et al. Mesenchymal stem cells inhibit natural killer–cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2, 3-dioxygenase and prostaglandin E2. Blood J Am Soc Hematol. 2008;111(3):1327–33.
Carreras-Planella L, et al. Immunomodulatory effect of MSC on B cells is independent of secreted extracellular vesicles. Front Immunol. 2019;10:1288.
Wilson A, et al. Isolation and characterisation of human adipose-derived stem cells. In: Immunological tolerance. Springer; 2019. p. 3–13.
Zhang F, et al. Mesenchymal stem cells alleviate rat diabetic nephropathy by suppressing CD103+ DCs-mediated CD8+ T cell responses. J Cell Mol Med. 2020;24(10):5817–31.
Feng Y, Li F, Yan J, Guo X, Wang F, Shi H, Du J, Zhang H, Gao Y, Li D, Yao Y, Hu W, Han J, Zhang M, Ding R, Wang X, Huang C, Zhang J. Pan-cancer analysis and experiments with cell lines reveal that the slightly elevated expression of DLGAP5 is involved in clear cell renal cell carcinoma progression. Life Sciences. 2021;287:120056
Xu L-L, et al. Impaired function of bone marrow mesenchymal stem cells from immune thrombocytopenia patients in inducing regulatory dendritic cell differentiation through the Notch-1/Jagged-1 signaling pathway. Stem cells Dev. 2017;26(22):1648–61.
Jiang X-X, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 2005;105(10):4120–6.
Liu Q, et al. Human mesenchymal stromal cells enhance the immunomodulatory function of CD8+ CD28− regulatory T cells. Cell Mol Immunol. 2015;12(6):708–18.
El Omar R, et al. Immunomodulation of endothelial differentiated mesenchymal stromal cells: impact on T and NK cells. Immunol Cell Biol. 2016;94(4):342–56.
Cho K-A, et al. Mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner. Cell Mol Immunol. 2017;14(11):895–908.
Liu X, et al. Mesenchymal stem/stromal cells induce the generation of novel IL-10–dependent regulatory dendritic cells by SOCS3 activation. J Immunol. 2012;189(3):1182–92.
Ahmed AU, et al. Bone marrow mesenchymal stem cells loaded with an oncolytic adenovirus suppress the anti-adenoviral immune response in the cotton rat model. Mol Ther. 2010;18(10):1846–56.
Komarova S, et al. Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses. Mol Cancer Ther. 2006;5(3):755–66.
Stoff-Khalili MA, et al. Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma. Breast Cancer Res Treat. 2007;105(2):157–67.
Sonabend AM, et al. Mesenchymal stem cells effectively deliver an oncolytic adenovirus to intracranial glioma. Stem cells. 2008;26(3):831–41.
Yong RL, et al. Human bone marrow–derived mesenchymal stem cells for intravascular delivery of oncolytic adenovirus Δ24-RGD to human gliomas. Cancer Res. 2009;69(23):8932–40.
Ahmed AU, et al. A comparative study of neural and mesenchymal stem cell-based carriers for oncolytic adenovirus in a model of malignant glioma. Mol Pharm. 2011;8(5):1559–72.
Mader EK, et al. Optimizing patient derived mesenchymal stem cells as virus carriers for a phase I clinical trial in ovarian cancer. J Transl Med. 2013;11(1):20.
Ong H-T, et al. Systemically delivered measles virus-infected mesenchymal stem cells can evade host immunity to inhibit liver cancer growth. J Hepatol. 2013;59(5):999–1006.
Klopp AH, et al. Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem cells. 2011;29(1):11–9.
Chulpanova DS, et al. Application of mesenchymal stem cells for therapeutic agent delivery in anti-tumor treatment. Front Pharmacol. 2018;9:259.
Aliyari-Serej Z, et al. Relation between Immune cell response and stemness genes expression in breast cancer; a new approach in NANOG gene and Let7-a expression in breast cancer cell lines. Immunopathol Persa. 2020;6(2):e21.
Sun B, et al. Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy. 2009;11(3):289–98.
Sui X, Zhang R, Liu S, Duan T, Zhai L, Zhang M, Han X, **ang Y, Huang X, Lin H, **e T. RSL3 drives ferroptosis through GPX4 inactivation and ROS production in colorectal cancer. Front Pharmacol. 2018. https://doi.org/10.3389/fphar.2018.01371
Otsu K, et al. Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells. Blood J Am Soc Hematol. 2009;113(18):4197–205.
Khakoo AY, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med. 2006;203(5):1235–47.
Kucerova L, et al. Tumor-driven molecular changes in human mesenchymal stromal cells. Cancer Microenviron. 2015;8(1):1–14. https://doi.org/10.1007/s12307-014-0151-9.
Cavarretta IT, et al. Adipose tissue–derived mesenchymal stem cells expressing prodrug-converting enzyme inhibit human prostate tumor growth. Mol Ther. 2010;18(1):223–31.
Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015;14(9):642–62.
Gujar S, et al. Antitumor benefits of antiviral immunity: an underappreciated aspect of oncolytic virotherapies. Trends Immunol. 2018;39(3):209–21.
De Matos AL, Franco LS, McFadden G. Oncolytic viruses and the immune system: the dynamic duo. Mol Ther Methods Clin Dev. 2020;17:349–58.
Liu S, Li Q, Chen K, Zhang Q, Li G, Zhuo L, Zhai B, Sui X, Hu X, **e T. The emerging molecular mechanism of m6A modulators in tumorigenesis and cancer progression. Biomed Pharmacother. 2020;127:110098. https://doi.org/10.1016/j.biopha.2020.110098.
Jhawar SR, et al. Oncolytic viruses—natural and genetically engineered cancer immunotherapies. Front Oncol. 2017;7:202.
Mullen JT, Tanabe KK. Viral oncolysis. Oncologist. 2002;7(2):106–19.
Hamid O, et al. Oncolytic immunotherapy: unlocking the potential of viruses to help target cancer. Cancer Immunol Immunother. 2017;66(10):1249–64.
Serrano-del Valle A, et al. Immunogenic cell death and immunotherapy of multiple myeloma. Front Cell Dev Biol. 2019;7:50.
Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12(1):31–46.
Guo ZS, Liu Z, Bartlett DL. Oncolytic immunotherapy: dying the right way is a key to eliciting potent antitumor immunity. Front Oncol. 2014;4:74.
Aaes TL, et al. Vaccination with necroptotic cancer cells induces efficient anti-tumor immunity. Cell Rep. 2016;15(2):274–87.
Wiernicki B, et al. Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity. Nat Commun. 2022;13(1):3676.
Pol JG, Bridle BW, Lichty BD. Detection of tumor antigen-specific T-cell responses after oncolytic vaccination. In: Oncolytic Viruses. Springer; 2020. p. 191–211.
Keshavarz M, et al. Oncolytic paramyxoviruses-induced autophagy; a prudent weapon for cancer therapy. J Biomed Sci. 2019;26(1):48.
Sobol PT, et al. Adaptive antiviral immunity is a determinant of the therapeutic success of oncolytic virotherapy. Mol Ther. 2011;19(2):335–44.
Workenhe ST, Verschoor ML, Mossman KL. The role of oncolytic virus immunotherapies to subvert cancer immune evasion. Future Oncol. 2015;11(4):675–89.
van Vloten JP, et al. Critical interactions between immunogenic cancer cell death, oncolytic viruses, and the immune system define the rational design of combination immunotherapies. J Immunol. 2018;200(2):450–8.
Marelli G, et al. Oncolytic viral therapy and the immune system: a double-edged sword against cancer. Front Immunol. 2018;9:866.
Bai Y, et al. Updates to the antitumor mechanism of oncolytic virus. Thorac Cancer. 2019;10(5):1031–5.
Garg AD, Agostinis P. Cell death and immunity in cancer: from danger signals to mimicry of pathogen defense responses. Immunol Rev. 2017;280(1):126–48.
Jiang H, Fueyo J. Healing after death: antitumor immunity induced by oncolytic adenoviral therapy. Oncoimmunology. 2014;3(7): e947872.
Jamali S, et al. Prevalence of malignancy and chronic obstructive pulmonary disease among patients with COVID-19: a systematic review and meta-analysis. Int J Sci Res Dent Med Sci. 2020;2(2):52–8.
Zhang Z, Cui F, Cao C, Wang Q, Zou Q. Single-cell RNA analysis reveals the potential risk of organ-specific cell types vulnerable to SARS-CoV-2 infections. Comput Biol Med 2022;140:105092. https://doi.org/10.1016/j.compbiomed.2021.105092.
Xu Q, et al. Evaluation of Newcastle disease virus mediated dendritic cell activation and cross-priming tumor-specific immune responses ex vivo. Int J Cancer. 2020;146(2):531–41.
Kepp O, et al. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology. 2014;3(9): e955691.
Reale A, et al. Perspectives on immunotherapy via oncolytic viruses. Infect Agents Cancer. 2019;14(1):5.
Filley AC, Dey M. Immune system, friend or foe of oncolytic virotherapy? Front Oncol. 2017;7:106.
Prestwich RJ, et al. Oncolytic viruses: a novel form of immunotherapy. Expert Rev Anticancer Ther. 2008;8(10):1581–8.
Harrington K, et al. Optimizing oncolytic virotherapy in cancer treatment. Nat Rev Drug Discovery. 2019;18(9):689–706.
Rotte A, ** J, Lemaire V. Mechanistic overview of immune checkpoints to support the rational design of their combinations in cancer immunotherapy. Ann Oncol. 2018;29(1):71–83.
Cai L, et al. Defective HLA class I antigen processing machinery in cancer. Cancer Immunol Immunother. 2018;67(6):999–1009.
Gujar S, et al. Multifaceted therapeutic targeting of ovarian peritoneal carcinomatosis through virus-induced immunomodulation. Mol Ther. 2013;21(2):338–47.
Lapteva N, et al. Attraction and activation of dendritic cells at the site of tumor elicits potent antitumor immunity. Mol Ther. 2009;17(9):1626–36.
Greiner S, et al. The highly attenuated vaccinia virus strain modified virus Ankara induces apoptosis in melanoma cells and allows bystander dendritic cells to generate a potent anti-tumoral immunity. Clin Exp Immunol. 2006;146(2):344–53.
Guillerme J-B, et al. Measles virus vaccine-infected tumor cells induce tumor antigen cross-presentation by human plasmacytoid dendritic cellscross-presentation of human tumor antigen by pDC. Clin Cancer Res. 2013;19(5):1147–58.
Benencia F, et al. Herpes virus oncolytic therapy reverses tumor immune dysfunction and facilitates tumor antigen presentation. Cancer Biol Ther. 2008;7(8):1194–205.
Denton NL, et al. Tumor-associated macrophages in oncolytic virotherapy: friend or foe? Biomedicines. 2016;4(3):13.
Marchini A. et al., Immune conversion of tumor microenvironment by oncolytic viruses: the protoparvovirus H-1PV case study. Front Immunol 2019: p. 1848.
Denton NL, et al. Myelolytic treatments enhance oncolytic herpes virotherapy in models of Ewing sarcoma by modulating the immune microenvironment. Mol Ther Oncolytics. 2018;11:62–74.
Tan DQ, et al. Macrophage response to oncolytic paramyxoviruses potentiates virus-mediated tumor cell killing. Eur J Immunol. 2016;46(4):919–28.
Ehrig K, et al. Growth inhibition of different human colorectal cancer xenografts after a single intravenous injection of oncolytic vaccinia virus GLV-1h68. J Transl Med. 2013;11(1):79.
Saha D, Martuza RL, Rabkin SD. Macrophage polarization contributes to glioblastoma eradication by combination immunovirotherapy and immune checkpoint blockade. Cancer Cell. 2017;32(2):253-267. e5.
Russell L, et al. Oncolytic viruses: priming time for cancer immunotherapy. BioDrugs. 2019;33(5):485–501.
** HY, Wang ZA. Global stabilization of the full attraction-repulsion Keller-Segel system. Discrete Contin Dyn Syst Ser A. 2020;40(6):3509–27. https://doi.org/10.3934/dcds.2020027.
Dharwadkar A, et al. Cytological study of salivary gland lesions along with histopathological correlation in a Tertiary Care Centre. Int J Sci Res Den Med Scis. 2022;4(3):101–9.
Hashemi Goradel N, et al. Nanoparticles as new tools for inhibition of cancer angiogenesis. J Cell Physiol. 2018;233(4):2902–10.
Goradel NH, et al. Melatonin as an angiogenesis inhibitor to combat cancer: mechanistic evidence. Toxicol Appl Pharmacol. 2017;335:56–63.
Angarita FA, et al. Mounting a strategic offense: fighting tumor vasculature with oncolytic viruses. Trends Mol Med. 2013;19(6):378–92.
Breitbach CJ, et al. Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans. Cancer Res. 2013;73(4):1265–75.
Bejarano MT, Merchan JR. Targeting tumor vasculature through oncolytic virotherapy: recent advances. Oncolytic Virother. 2015;4:169.
Hammoud A, Tikhomirov AN, Shaheen Z. Automatic bio-impedance signal analysis: smoothing processes efficacy evaluation in determining the vascular tone type. In: 2021 Ural symposium on biomedical engineering, radioelectronics and information technology (USBEREIT). IEEE. 2021. pp. 0113–0116.
Haka AS, et al. In vivo margin assessment during partial mastectomy breast surgery using Raman spectroscopy. Cancer Res. 2006;66(6):3317–22.
Breitbach CJ, et al. Targeted inflammation during oncolytic virus therapy severely compromises tumor blood flow. Mol Ther. 2007;15(9):1686–93.
Hammoud A, Tikhomirov A, Myasishcheva G, Shaheen Z, Volkov A, Briko A, Shchukin S. Multi-channel bioimpedance system for detecting vascular tone in human limbs: an approach. Sensors (Basel, Switzerland) 2021;22(1):138. https://doi.org/10.3390/s22010138.
Russell SJ, Peng K-W, Bell JC. Oncolytic virotherapy. Nat Biotechnol. 2012;30(7):658–70.
Alemany R, Balagué C, Curiel DT. Replicative adenoviruses for cancer therapy. Nat Biotechnol. 2000;18(7):723–7.
Nettelbeck DM. Virotherapeutics: conditionally replicative adenoviruses for viral oncolysis. Anticancer Drugs. 2003;14(8):577–84.
Yamamoto M, Curiel DT. Current issues and future directions of oncolytic adenoviruses. Mol Ther. 2010;18(2):243–50.
Pol J, et al. Trial Watch: oncolytic viruses for cancer therapy. Oncoimmunology. 2014;3: e28694.
He X, Zhu Y, Yang L, Wang Z, Wang Z, Feng J, Wen X, Cheng L, Zhu R. MgFe-LDH nanoparticles: a promising leukemia inhibitory factor replacement for self-renewal and pluripotency maintenance in cultured mouse embryonic stem cells. Adv Sci (Weinheim, Baden-Wurttemberg, Germany). 2021;8(9):2003535. https://doi.org/10.1002/advs.202003535.
Bramante S, et al. Serotype chimeric oncolytic adenovirus coding for GM-CSF for treatment of sarcoma in rodents and humans. Int J Cancer. 2014;135(3):720–30.
Liikanen I, et al. Oncolytic adenovirus with temozolomide induces autophagy and antitumor immune responses in cancer patients. Mol Ther. 2013;21(6):1212–23.
Kanerva A, et al. Antiviral and antitumor T-cell immunity in patients treated with GM-CSF–coding oncolytic adenovirus. Clin Cancer Res. 2013;19(10):2734–44.
Kim KH, et al. A phase I clinical trial of Ad5/3-Δ24, a novel serotype-chimeric, infectivity-enhanced, conditionally-replicative adenovirus (CRAd), in patients with recurrent ovarian cancer. Gynecol Oncol. 2013;130(3):518–24.
Bramante S, et al. Treatment of melanoma with a serotype 5/3 chimeric oncolytic adenovirus coding for GM-CSF: Results in vitro, in rodents and in humans. Int J Cancer. 2015;137(7):1775–83.
Garcia-Castro J, et al. Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study. Cancer Gene Ther. 2010;17(7):476–83.
Barahman M, Bahadoram M, Mahmoudian-Sani M. Frequency of triple negative breast cancer in referrals patients to an oncology radiotherapy section. J Prev Epidemiol. 2021;6(1): e09.
Khalili SM, et al. Comparing the quality of life of women suffering from breast cancer receiving palliative care and ordinary care. Immunopathol Persa. 2020;6(2):e22.
Sadr Z, et al. Study of family medicine role in breast cancer prevention: a systematic review. J Prev Epidemiol. 2021;6(2):e32–e32.
Fouladi N, et al. Factors associated with delayed diagnosis of breast cancer; a study in North-West of Iran. Immunopathol Persa. 2019;6(1):e02.
Darakhshandeh A, Momenzadeh M. Cachexia and anorexia in cancer; a systematic review. Immunopathol Persa. 2020;7(2):e20.
Rincón E, et al. Mesenchymal stem cell carriers enhance antitumor efficacy of oncolytic adenoviruses in an immunocompetent mouse model. Oncotarget. 2017;8(28):45415.
Guo Y, et al. Menstrual blood-derived stem cells as delivery vehicles for oncolytic adenovirus virotherapy for colorectal cancer. Stem cells Dev. 2019;28(13):882–96.
Kaczorowski A, et al. Delivery of improved oncolytic adenoviruses by mesenchymal stromal cells for elimination of tumorigenic pancreatic cancer cells. Oncotarget. 2016;7(8):9046.
Chastkofsky MI, et al. Mesenchymal stem cells successfully deliver oncolytic virotherapy to diffuse intrinsic pontine GliomaStem cells deliver virotherapy to DIPG. Clin Cancer Res. 2021;27(6):1766–77.
Shomali N, et al. Survivin; a novel therapeutic target that correlates with survival of autoreactive T lymphocytes obtained from patients with ankylosing spondylitis. Gene. 2022;844: 146829.
Shomali N, et al. Dysregulation of survivin-targeting microRNAs in autoimmune diseases: new perspectives for novel therapies. Front Immunol. 2022;13: 839945.
Zhang Y, et al. Therapeutic effects of mesenchymal stem cells loaded with oncolytic adenovirus carrying decorin on a breast cancer lung metastatic mouse model. Mol Ther Oncolytics. 2022;24:486–96.
Zhang J, et al. Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying IL-24/endostatin enhances glioma therapy. Cancer Lett. 2021;509:26–38.
Du W, et al. Stem cell-released oncolytic herpes simplex virus has therapeutic efficacy in brain metastatic melanomas. Proc Natl Acad Sci. 2017;114(30):E6157–65.
Duebgen M, et al. Stem cells loaded with multimechanistic oncolytic herpes simplex virus variants for brain tumor therapy. JNCI J Natl Cancer Inst. 2014;106(6):dju090.
Castleton A, et al. Human mesenchymal stromal cells deliver systemic oncolytic measles virus to treat acute lymphoblastic leukemia in the presence of humoral immunity. Blood J Am Soc Hematol. 2014;123(9):1327–35.
Josiah DT, et al. Adipose-derived stem cells as therapeutic delivery vehicles of an oncolytic virus for glioblastoma. Mol Ther. 2010;18(2):377–85.
Jazowiecka-Rakus J, et al. Myxoma virus-loaded mesenchymal stem cells in experimental oncolytic therapy of murine pulmonary melanoma. Mol Ther Oncol. 2020;18:335–50.
Jazowiecka-Rakus J, et al. Myxoma virus expressing LIGHT (TNFSF14) pre-loaded into adipose-derived mesenchymal stem cells is effective treatment for murine pancreatic adenocarcinoma. Cancers. 2021;13(6):1394.
Jazowiecka-Rakus J, et al. Combination of LIGHT (TNFSF14)-armed myxoma virus pre-loaded into ADSCs and gemcitabine in the treatment of experimental orthotopic murine pancreatic adenocarcinoma. Cancers. 2022;14(8):2022.
Babaei A, et al. Mesenchymal stem cells loaded with oncolytic reovirus enhances antitumor activity in mice models of colorectal cancer. Biochem Pharmacol. 2021;190: 114644.
Banijamali RS, et al. Mesenchymal stem cells support delivery and boost the efficacy of oncolytic reoviruses in TC-1 tumor cells. J Cell Biochem. 2021;122(10):1360–75.
Wang X, et al. Mesenchymal stem cell carriers enhance antitumor efficacy induced by oncolytic reovirus in acute myeloid leukemia. Int Immunopharmacol. 2021;94: 107437.
Barlabé P, et al. Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers. Cancer Gene Ther. 2020;27(5):383–8.
Ho C-T, et al. Combination of mesenchymal stem cell-delivered oncolytic virus with prodrug activation increases efficacy and safety of colorectal cancer therapy. Biomedicines. 2021;9(5):548.
Keshavarz A, et al. Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies. Stem Cell Res Ther. 2022;13(1):482.
Mardi A, et al. 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 Int. 2022;22(1):169.
McKenna MK, et al. Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity. Mol Ther. 2021;29(5):1808–20.
Darwish MM, et al. Prognostic implication of PD-L1 expression and associated tumor infiltrating lymphocytes in metastatic breast cancer. Immunopathol Persa. 2021;8(1):e18.
Sorkhabi AD, et al. Cancer combination therapies by silencing of CTLA-4, PD-L1, and TIM3 in osteosarcoma. IUBMB Life. 2022;74(9):908–17.
Rahimi Kalateh Shah Mohammad G, et al. Cytokines as potential combination agents with PD-1/PD-L1 blockade for cancer treatment. J Cell Physiol. 2020;235(7–8):5449–60.
Varghese S, Rabkin SD. Oncolytic herpes simplex virus vectors for cancer virotherapy. Cancer Gene Ther. 2002;9(12):967–78.
Hoffmann D, Wildner O. Comparison of herpes simplex virus-and conditionally replicative adenovirus-based vectors for glioblastoma treatment. Cancer Gene Ther. 2007;14(7):627–39.
Msaouel P, Dispenzieri A, Galanis E. Clinical testing of engineered oncolytic measles virus strains in the treatment of cancer: an overview. Curr Opin Mol Ther. 2009;11(1):43.
Lech PJ, Russell SJ. Use of attenuated paramyxoviruses for cancer therapy. Expert Rev Vaccines. 2010;9(11):1275–302.
Dai X-M, et al. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood J Am Soc Hematol. 2002;99(1):111–20.
Künzi V, et al. Recombinant measles virus induces cytolysis of cutaneous T-cell lymphoma in vitro and in vivo. J Investig Dermatol. 2006;126(11):2525–32.
Peng K-W, et al. Systemic therapy of myeloma xenografts by an attenuated measles virus. Blood J Am Soc Hematol. 2001;98(7):2002–7.
Peng K-W, et al. Intraperitoneal therapy of ovarian cancer using an engineered measles virus. Cancer Res. 2002;62(16):4656–62.
Phuong LK, et al. Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme. Cancer Res. 2003;63(10):2462–9.
Blechacz B, et al. Engineered measles virus as a novel oncolytic viral therapy system for hepatocellular carcinoma. Hepatology. 2006;44(6):1465–77.
Liu C, et al. Prostate-specific membrane antigen retargeted measles virotherapy for the treatment of prostate cancer. Prostate. 2009;69(10):1128–41.
Yazdani A, et al. Evaluation of the urine mRNA-PCA3 expression level in prostate patients; comparison between benign prostatic hyperplasia and cancer. Immunopathol Persa. 2022;8(2):e15207–e15207.
Iankov ID, et al. Demonstration of anti-tumor activity of oncolytic measles virus strains in a malignant pleural effusion breast cancer model. Breast Cancer Res Treat. 2010;122(3):745–54.
Wang B, et al. Deficiency of caspase 3 in tumor xenograft impairs therapeutic effect of measles virus Edmoston strain. Oncotarget. 2015;6(18):16019.
Lv Y, et al. A recombinant measles virus vaccine strain rMV-Hu191 has oncolytic effect against human gastric cancer by inducing apoptotic cell death requiring integrity of lipid raft microdomains. Cancer Lett. 2019;460:108–18.
Hasanpour Dehkordi A, Keikhaei B, Bahadoram M, Razmjoo S, Barahman M. Keep the corners; impact of chemotherapy on renal function. J Nephropathol. 2020;9(1):e02.
Gauvrit A, et al. Measles virus induces oncolysis of mesothelioma cells and allows dendritic cells to cross-prime tumor-specific CD8 response. Cancer res. 2008;68(12):4882–92.
Zhao D, et al. Live attenuated measles virus vaccine induces apoptosis and promotes tumor regression in lung cancer. Oncol Rep. 2013;29(1):199–204.
McDonald CJ, et al. A measles virus vaccine strain derivative as a novel oncolytic agent against breast cancer. Breast Cancer Res Treat. 2006;99(2):177–84.
Lampe J, et al. An armed oncolytic measles vaccine virus eliminates human hepatoma cells independently of apoptosis. Gene Ther. 2013;20(11):1033–41.
Donnelly OG, et al. Measles virus causes immunogenic cell death in human melanoma. Gene Ther. 2013;20(1):7–15.
Hall K, et al. Reovirus-mediated cytotoxicity and enhancement of innate immune responses against acute myeloid leukemia. BioResearch Open Access. 2012;1(1):3–15.
Chakrabarty R, et al. The oncolytic virus, pelareorep, as a novel anticancer agent: a review. Investig New Drugs. 2015;33(3):761–74.
Ferhat M. Oncolytic viruses: the next major breakthrough in cancer treatment. J Hum Virol Retrovirol. 2017;5(1):00141.
Li J, Zhao J, Tan T, Liu M, Zeng Z, Zeng Y, Zhang L, Fu C, Chen D, **e T. Nanoparticle drug delivery system for glioma and its efficacy improvement strategies: a comprehensive review. Int J Nanomed. 2020;15:2563–82. https://doi.org/10.2147/IJN.S243223.
Babaei A, et al. In vitro anti-cancer activity of adipose-derived mesenchymal stem cells increased after infection with oncolytic reovirus. Adv Pharm Bull. 2021;11(2):361.
Kaneko Y, et al. Bone marrow-derived stem cell therapy for metastatic brain cancers. Cell Transplant. 2015;24(4):625–30.
Khosravian M, Momenzadeh M, Koosha F, Alimohammadi N, Kianpour N. Lung cancer risk and the inhibitors of angiotensin converting enzyme; an updated review on recent evidence. Immunopathol Persa. 2022;8(1):e19.
Yulyana Y, et al. Paracrine factors of human fetal MSCs inhibit liver cancer growth through reduced activation of IGF-1R/PI3K/Akt signaling. Mol Ther. 2015;23(4):746–56.
Lin HD, et al. Human umbilical cord wharton’s jelly stem cell conditioned medium induces tumoricidal effects on lymphoma cells through hydrogen peroxide mediation. J Cell Biochem. 2016;117(9):2045–55.
Lin W, et al. Mesenchymal stem cells and cancer: clinical challenges and opportunities. BioMed Res Int. 2019;2019:2820853.
Block GJ, et al. Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1. Stem cells. 2009;27(3):670–81.
Sakaida I, et al. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology. 2004;40(6):1304–11.
Wang L, et al. Hepatic vascular endothelial growth factor regulates recruitment of rat liver sinusoidal endothelial cell progenitor cells. Gastroenterology. 2012;143(6):1555-1563. E2.
Kim SU, et al. The Laennec staging system for histological sub-classification of cirrhosis is useful for stratification of prognosis in patients with liver cirrhosis. J Hepatol. 2012;57(3):556–63.
Spaeth EL, et al. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS ONE. 2009;4(4): e4992.
Feng B, Chen L. Review of mesenchymal stem cells and tumors: executioner or coconspirator? Cancer Biother Radiopharm. 2009;24(6):717–21.
Du WJ, et al. Heterogeneity of proangiogenic features in mesenchymal stem cells derived from bone marrow, adipose tissue, umbilical cord, and placenta. Stem Cell Res Ther. 2016;7(1):163.
Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16(9):582–98.
Ishihara S, et al. Mechano-signal transduction in mesenchymal stem cells induces prosaposin secretion to drive the proliferation of breast cancer cells. Cancer Res. 2017;77(22):6179–89.
Barcellos-de-Souza P, et al. Mesenchymal stem cells are recruited and activated into carcinoma-associated fibroblasts by prostate cancer microenvironment-derived TGF-β1. Stem cells. 2016;34(10):2536–47.
Martin F, et al. Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Res Treat. 2010;124(2):317–26.
Xue Z, et al. Mesenchymal stem cells promote epithelial to mesenchymal transition and metastasis in gastric cancer though paracrine cues and close physical contact. J Cell Biochem. 2015;116(4):618–27.
Shahverdi M, et al. The regulatory role of autophagy-related miRNAs in lung cancer drug resistance. Biomed Pharmacother. 2022;148: 112735.
Jafari M, et al. Tempol effect on epithelial-mesenchymal transition induced by hyperglycemia. J Nephropathol. 2017;6(1):1–4.
Karnoub AE, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449(7162):557–63.
McAndrews KM, et al. Mesenchymal stem cells induce directional migration of invasive breast cancer cells through TGF-β. Sci Rep. 2015;5(1):16941.
Eckert F, et al. Potential role of CXCR4 targeting in the context of radiotherapy and immunotherapy of cancer. Front Immunol. 2018;9:3018.
Ma M, et al. Mesenchymal stromal cells may enhance metastasis of neuroblastoma via SDF-1/CXCR4 and SDF-1/CXCR7 signaling. Cancer Lett. 2011;312(1):1–10. https://doi.org/10.1016/j.canlet.2011.06.028.
Zemp FJ, et al. Cellular factors promoting resistance to effective treatment of glioma with oncolytic myxoma virus. Cancer Res. 2014;74(24):7260–73.
Peng K, et al. Using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses. Gene Ther. 2013;20(3):255–61.
Ferguson MS, Lemoine NR, Wang Y, Systemic delivery of oncolytic viruses: hopes and hurdles. Adv Virol. 2012. 2012.
Gao Y, Zhang H, Lirussi F, Garrido C, Ye X, **e T. Dual inhibitors of histone deacetylases and other cancerrelated targets: a pharmacological perspective. Biochem Pharmacol. 2020;182:114224. https://doi.org/10.1016/j.bcp.2020.114224.
Otsuki A, et al. Histone deacetylase inhibitors augment antitumor efficacy of herpes-based oncolytic viruses. Mol Ther. 2008;16(9):1546–55.
Cody JJ, Markert JM, Hurst DR. Histone deacetylase inhibitors improve the replication of oncolytic herpes simplex virus in breast cancer cells. PLoS ONE. 2014;9(3): e92919.
Sadler AJ, Williams BR. Interferon-inducible antiviral effectors. Nat Rev Immunol. 2008;8(7):559–68.
Jha BK, et al. Inhibition of RNase L and RNA-dependent protein kinase (PKR) by sunitinib impairs antiviral innate immunity. J Biol Chem. 2011;286(30):26319–26.
Bell J, McFadden G. Viruses for tumor therapy. Cell Host Microbe. 2014;15(3):260–5.
Moreno R, et al. Enhanced antitumor efficacy of Oncolytic adenovirus–loaded menstrual blood–derived Mesenchymal stem cells in combination with peripheral blood mononuclear cells. Mol Cancer Ther. 2019;18(1):127–38.
Thaci B, et al. Pharmacokinetic study of neural stem cell-based cell carrier for oncolytic virotherapy: targeted delivery of the therapeutic payload in an orthotopic brain tumor model. Cancer Gene Ther. 2012;19(6):431–42.
Roth J, Curiel D, Pereboeva L. Cell vehicle targeting strategies. Gene Ther. 2008;15(10):716–29.
Arbab AS, et al. In vivo trafficking and targeted delivery of magnetically labeled stem cells. Hum Gene Ther. 2004;15(4):351–60.
Fiarresga A, et al. Intracoronary delivery of human mesenchymal/stromal stem cells: insights from coronary microcirculation invasive assessment in a swine model. PLoS ONE. 2015;10(10): e0139870.
Silva LH, et al. Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells. Stem Cell Res Ther. 2017;8(1):58.
Kauer TM, et al. Encapsulated therapeutic stem cells implanted in the tumor resection cavity induce cell death in gliomas. Nat Neurosci. 2012;15(2):197–204.
Shah K. Encapsulated stem cells for cancer therapy. Biomatter. 2013;3(1): e24278.
Sanchez-Diaz M, et al. Biodistribution of mesenchymal stromal cells after administration in animal models and humans: a systematic review. J Clin Med. 2021;10(13):2925.
Hammoud A, Sharay EY, Tikhomirov AN. Newtonian and non-Newtonian pulsatile flows through carotid artery bifurcation based on CT image geometry. In: AIP Conference Proceedings, Vol. 2171. AIP Publishing LLC. 2019. P. 110022.
Schrepfer S, et al. Stem cell transplantation: the lung barrier. In: Transplantation proceedings. Elsevier. 2007.
Rosenblum D, et al. Progress and challenges towards targeted delivery of cancer therapeutics. Nat Commun. 2018;9(1):1410.
Hooshyar N, Hassanzadeh S, Nasri H. Acute and chronic kidney disease in lung cancer; an update. J Ren Endocrinol. 2018;4:e22.
De Becker A, Van Riet I. Homing and migration of mesenchymal stromal cells: how to improve the efficacy of cell therapy? World J Stem Cells. 2016;8(3):73.
Yumul R, et al. Epithelial junction opener improves oncolytic adenovirus therapy in mouse tumor models. Hum Gene Ther. 2016;27(4):325–37.
Turley EA, et al. Mechanisms of disease: epithelial–mesenchymal transition—does cellular plasticity fuel neoplastic progression? Nat Clin Pract Oncol. 2008;5(5):280–90.
Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer res. 2006;66(17):8319–26.
Wojton J, Kaur B. Impact of tumor microenvironment on oncolytic viral therapy. Cytokine Growth Factor Rev. 2010;21(2–3):127–34.
Kuriyama N, et al. Pretreatment with protease is a useful experimental strategy for enhancing adenovirus-mediated cancer gene therapy. Hum Gene Ther. 2000;11(16):2219–30.
de Heer P, et al. Cyclooxygenase 2 expression in rectal cancer is of prognostic significance in patients receiving preoperative radiotherapy. Clin Cancer Res. 2007;13(10):2955–60.
Mok W, Boucher Y, Jain RK. Matrix metalloproteinases-1 and-8 improve the distribution and efficacy of an oncolytic virus. Cancer res. 2007;67(22):10664–8.
Nagano S, et al. Cancer cell death enhances the penetration and efficacy of oncolytic herpes simplex virus in tumors. Cancer res. 2008;68(10):3795–802.
Wong HH, Lemoine NR, Wang Y. Oncolytic viruses for cancer therapy: overcoming the obstacles. Viruses. 2010;2(1):78–106.
Shen B, Hermiston T. Effect of hypoxia on Ad5 infection, transgene expression and replication. Gene Ther. 2005;12(11):902–10.
Shen B, Bauzon M, Hermiston T. The effect of hypoxia on the uptake, replication and lytic potential of group B adenovirus type 3 (Ad3) and type 11p (Ad11p). Gene Ther. 2006;13(12):986–90.
Hernandez-Alcoceba R, et al. New oncolytic adenoviruses with hypoxia-and estrogen receptor-regulated replication. Hum Gene Ther. 2002;13(14):1737–50.
Aghi MK, et al. Hypoxia enhances the replication of oncolytic herpes simplex virus. Mol Ther. 2009;17(1):51–6.
Fasullo M, Burch A, Britton A. Hypoxia enhances the replication of oncolytic herpes simplex virus in p53-breast cancer cells. Cell Cycle. 2009;8(14):2194–7.
Dinita Devi N, et al. Askin tumor: a case report of a rare tumor. Int J Sci Res Dent Med Sci. 2021;3(3):153–5.
Shariati Y, et al. Evaluate the clinical outcome of nanoparticle albumin-bound paclitaxel on breast cancer treatment: a systematic review and meta-analysis. Int J Sci Res Dent Med Sci. 2022;4(3):127–33.
Bagó JR, Sheets KT, Hingtgen SD. Neural stem cell therapy for cancer. Methods. 2016;99:37–43.
Zielske SP, Livant DL, Lawrence TS. Radiation increases invasion of gene-modified mesenchymal stem cells into tumors. Int J Radiat Oncol Biol Phys. 2009;75(3):843–53.
Kubo H, et al. Phase I dose escalation clinical trial of adenovirus vector carrying osteocalcin promoter-driven herpes simplex virus thymidine kinase in localized and metastatic hormone-refractory prostate cancer. Hum Gene Ther. 2003;14(3):227–41.
Alvarez RD, Curiel DT. A phase I study of recombinant adenovirus vector-mediated intraperitoneal delivery of herpes simplex virus thymidine kinase (HSV-TK) gene and intravenous ganciclovir for previously treated ovarian and extraovarian cancer patients. University of Alabama Comprehensive Cancer Center, Birmingham, AL. Hum Gene Ther. 1997;8(5):597–613.
Hu S, Hui Z, Lirussi F, Garrido C, Ye X, **e T. Small molecule DNA-PK inhibitors as potential cancer therapy: a patent review (2010–present). Expert Opin Ther Pat. 2021;31(5):435–52. https://doi.org/10.1080/13543776.2021.1866540.
De Graaf J, et al. Armed oncolytic viruses: A kick-start for anti-tumor immunity. Cytokine Growth Factor Rev. 2018;41:28–39.
Pearl TM, et al. Oncolytic virus-based cytokine expression to improve immune activity in brain and solid tumors. Mol Ther Oncolytics. 2019;13:14–21.
Twumasi-Boateng K, et al. Oncolytic viruses as engineering platforms for combination immunotherapy. Nat Rev Cancer. 2018;18(7):419–32.
Ocansey DKW, et al. Improved therapeutics of modified mesenchymal stem cells: an update. J Transl Med. 2020;18(1):42.
Zheng M, et al. Oncolytic viruses for cancer therapy: barriers and recent advances. Mol Ther Oncol. 2019;15:234–47.
Na Y, et al. Systemic administration of human mesenchymal stromal cells infected with polymer-coated oncolytic adenovirus induces efficient pancreatic tumor homing and infiltration. J Control Release. 2019;305:75–88.
Moreno R, et al., Human menstrual blood-derived mesenchymal stem cells as potential cell carriers for oncolytic adenovirus. Stem Cells Int 2017. 3615729.
Acknowledgements
Not applicable
Funding
No Funders.
Author information
Authors and Affiliations
Contributions
All authors contributed to the conception and the main idea of the work. NGD, AIG, MEA, AOZ, MJA, RSZ, MAJ, SAJA, and JAR drafted the main text, figures, and tables. MD supervised the work and provided the comments and additional scientific information. YSA, NMM, YFM, and RAS also reviewed and revised the text. All authors read and approved the final version of the work to be published.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
There is no conflict of interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
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 http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Ghasemi Darestani, N., Gilmanova, A.I., Al-Gazally, M.E. et al. Mesenchymal stem cell-released oncolytic virus: an innovative strategy for cancer treatment. Cell Commun Signal 21, 43 (2023). https://doi.org/10.1186/s12964-022-01012-0
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s12964-022-01012-0