Oncolytic viruses in lung cancer treatment: a review article.

Lung cancer has a high morbidity rate worldwide due to its resistance to therapy. So new treatment options are needed to improve the outcomes of lung cancer treatment. This study aimed to evaluate the effectiveness of oncolytic viruses (OVs) as a new type of cancer treatment. In this study, 158 articles from PubMed and Scopus from 1994 to 2022 were reviewed on the effectiveness of OVs in the treatment of lung cancer. The oncolytic properties of eight categories of OVs and their interactions with treatment options were investigated. OVs can be applied as a promising immunotherapy option, as they are reproduced selectively in different types of cancer cells, cause tumor cell lysis and trigger efficient immune responses.

A lot of research has been done to find a cure for lung cancer. Among the methods investigated is the treatment of cancer using a type of virus called an oncolytic virus (OV). Since tumors have unique properties, OVs tend to bind to them and activate immune cells to kill them. This article reviews the combination of OVs with other common cancer treatments which improves their effectiveness, causes fewer reactions and brings better results.

The antitumor effect of oncolytic respiratory syncytial virus via the tumor necrosis factor-alpha induction and ROS-bax-mediated mechanisms.

BACKGROUND: Cervical cancer represents one of the most prevalent cancers among women worldwide, particularly in low- and middle-income nations. Oncolytic viruses (OVs) can infect cancer cells selectively and lethally without harming normal cells. Respiratory syncytial virus (RSV) is an oncolytic virus for anticancer therapy because of its propensity to multiply within tumor cells. This research aimed to assess the in vitro antitumor activities and molecular basis processes of the oncolytic RSV-A2 on the TC-1 cancer cells as a model for HPV­related cervical cancers. METHODS: Cellular proliferation (MTT) and lactate dehydrogenase (LDH) release assays were used to investigate the catalytic impacts of RSV-A2 by the ELISA method. Real-time PCR and flow cytometry assays were utilized to assess apoptosis, autophagy, intracellular concentrations of reactive oxygen species (ROS), and cell cycle inhibition. RESULTS: Our MTT and LDH results demonstrated that TC-1 cell viability after oncolytic RSV-A2 treatment was MOI-dependently and altered significantly with increasing RSV-A2 virus multiplicity of infection (MOI). Other findings showed that the RSV-A2 potentially resulted in apoptosis and autophagy induction, caspase-3 activation, ROS generation, and cell cycle inhibition in the TC-1 cell line. Real-time PCR assay revealed that RSV-A2 infection significantly elevated the Bax and decreased the Bcl2 expression. CONCLUSIONS: The results indicated that oncolytic RSV-A2 has cytotoxic and inhibiting effects on HPV-associated cervical cancer cells. Our findings revealed that RSV-A2 is a promising treatment candidate for cervical cancer.

The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways.

Hepatocellular carcinoma (HCC) is a significant global health issue, with a high prevalence in many regions. There are variations in the etiology of HCC in different regions, but most cases are due to long-term infection with viral hepatitis. Hepatitis B virus (HBV) is responsible for more than 50% of virus-related HCC, which highlights the importance of HBV in pathogenesis of the disease. The development and progression of HBV-related HCC is a complex multistep process that can involve host, viral, and environmental factors. Several studies have suggested that some HBV genome mutations as well as HBV proteins can dysregulate cell signaling pathways involved in the development of HCC. Furthermore, it seems that the pathogenicity, progression of liver diseases, response to treatment and also viral replication are different among HBV mutants. Understanding the relationship between HBV genome variations and host signaling pathway alteration will improve our understanding of the molecular pathogenesis of HBV-related HCC. Furthermore, investigating commonly dysregulated pathways in HBV-related HCC is necessary to discover more specific therapeutic targets and develop more effective strategies for HCC treatment. The objective of this review is to address the role of HBV in the HCC progression and primarily focus on the impacts of HBV genome variations on HCC-related signaling pathways.

Interleukin-24-mediated antitumor effects against human glioblastoma via upregulation of P38 MAPK and endogenous TRAIL-induced apoptosis and LC3-II activation-dependent autophagy.

BACKGROUND: Melanoma differentiation-associated gene 7 (Mda-7) encodes IL-24, which can induce apoptosis in cancer cells. A novel gene therapy approach to treat deadly brain tumors, recombinant mda-7 adenovirus (Ad/mda-7) efficiently kills glioma cells. In this study, we investigated the factors affecting cell survival and apoptosis and autophagy mechanisms that destroy glioma cells by Ad/IL-24. METHODS: Human glioblastoma U87 cell line was exposed to a multiplicity of infections of Ad/IL-24. Antitumor activities of Ad/IL-24 were assessed by cell proliferation (MTT) and lactate dehydrogenase (LDH) release analysis. Using flow cytometry, cell cycle arrest and apoptosis were investigated. Using the ELISA method, the tumor necrosis factor (TNF-α) level was determined as an apoptosis-promoting factor and Survivin level as an anti-apoptotic factor. The expression levels of TNF-related apoptosis inducing ligand(TRAIL) and P38 MAPK genes were assessed by the Reverse transcription-quantitative polymerase chain reaction(RT­qPCR) method. The expression levels of caspase-3 and protein light chain 3-II (LC3-II) proteins were analyzed by flow cytometry as intervening factors in the processes of apoptosis and autophagy in the cell death signaling pathway, respectively. RESULTS: The present findings demonstrated that transduction of IL-24 inhibited cell proliferation and induced cell cycle arrest and cell apoptosis in glioblastoma. Compared with cells of the control groups, Ad/IL24-infected U87 cells exhibited significantly increased elevated caspase-3, and TNF-α levels, while the survivin expression was decreased. TRAIL was shown to be upregulated in tumor cells after Ad/IL-24 infection and studies of the apoptotic cascade regulators indicate that Ad/IL-24 could further enhance the activation of apoptosis through the TNF family of death receptors. In the current study, we demonstrate that P38 MAPK is significantly activated by IL-24 expression. In addition, the overexpression of mda-7/IL-24 in GBM cells induced autophagy, which was triggered by the upregulation of LC3-II. CONCLUSIONS: Our study demonstrates the antitumor effect of IL-24 on glioblastoma and may be a promising therapeutic approach for GBM cancer gene therapy.

Recombinant COVID-19 vaccine based on recombinant RBD/Nucleoprotein and saponin adjuvant induces long-lasting neutralizing antibodies and cellular immunity.

SARS-CoV-2 has caused a global pandemic, infecting millions of people. An effective preventive vaccine against this virus is urgently needed. Here, we designed and developed a novel formulated recombinant receptor-binding domain (RBD) nucleocapsid (N) recombinant vaccine candidates. The RBD and N were separately expressed in E. coli and purified using column chromatography. The female Balb/c mice were immunized subcutaneously with the combination of purified RBD and N alone or formulated with saponin adjuvant in a two-week interval in three doses. Neutralization antibody (Nabs) titers against the SARS-CoV-2 were detected by a Surrogate Virus Neutralization (sVNT) Test. Also, total IgG and IgG1, and IgG2a isotypes and the balance of cytokines in the spleen (IFN-γ, Granzyme B, IL-4, and IL-12) were measured by ELISA. The percentages of CD4+ and CD8+ T cells were quantified by flow cytometry. The lymphoproliferative activity of restimulated spleen cells was also determined. The findings showed that the combination of RBD and N proteins formulated with saponin significantly promoted specific total IgG and neutralization antibodies, elicited robust specific lymphoproliferative and T cell response responses. Moreover, marked increase in CD4+ and CD8+ T cells were observed in the adjuvanted RBD and N vaccine group compared with other groups. The results suggest that the formulations are able to elicit a specific long-lasting mixed Th1/Th2 balanced immune response. Our data indicate the significance of the saponin-adjuvanted RBD/N vaccine in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective long-lasting and strong vaccine.

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade.

BACKGROUND: MDA-7/IL-24 cytokine has shown potent antitumor properties in various types of cancer without exerting any significant toxicity on healthy cells. It has also been proved to encompass pro-immune Th1 cytokine-like behavior. Several E7 DNA vaccines have developed against human papillomavirus (HPV)-related cervical cancer. However, the restricted immunogenicity has limited their clinical applications individually. To address this deficiency, we investigated whether combining the E7 DNA vaccine with MDA-7/IL-24 as an adjuvant would elicit efficient antitumor responses in tumor-bearing mouse models. Next, we evaluated how suppression of immunosuppressive IL-10 cytokine would enhance the outcome of our candidate adjuvant vaccine. METHODS: For this purpose, tumor-bearing mice received either E7 DNA vaccine, MDA-7/IL-24 cytokine or combination of E7 vaccine with MDA-7/IL-24 adjuvant one week after tumor challenge and boosted two times with one-week interval. IL-10 blockade was performed by injection of anti-IL-10 mAb before each immunization. One week after the last immunization, mice were sacrificed and the treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, the condition of tumors was monitored every two days for six weeks intervals from week 2 on, and the tumor volume was measured and compared within different groups. RESULTS: A highly significant synergistic relationship was observed between the E7 DNA vaccine and the MDA-7/IL-24 cytokine against HPV-16+ cervical cancer models. An increase in proliferation of lymphocytes, cytotoxicity of CD8+ T cells, the level of Th1 cytokines (IFN-γ, TNF-α) and IL-4, the level of apoptotic markers (TRAIL and caspase-9), and a decrease in the level of immunosuppressive IL-10 cytokine, together with the control of tumor growth and the induction of tumor regression, all prove the efficacy of adjuvant E7&IL-24 vaccine when compared to their individual administration. Surprisingly, vaccination with the DNA E7&IL-24 significantly reduced the population of Regulatory T cells (Treg) in the spleen of immunized mice compared to sole administration and control groups. Moreover, IL-10 blockade enhanced the effect of the co-administration by eliciting higher levels of IFN-γ and caspase-9, reducing Il-10 secretion and provoking the regression of tumor size. CONCLUSION: The synergy between the E7 DNA vaccine and MDA-7/IL-24 suggests that DNA vaccines' low immunogenicity can be effectively addressed by coupling them with an immunoregulatory agent. Moreover, IL-10 blockade can be considered a complementary treatment to improve the outcome of conventional or novel cancer therapies.

Oncolytic virus delivery modulated immune responses toward cancer therapy: Challenges and perspectives.

Oncolytic viruses (OVs) harness the hallmarks of tumor cells and cancer-related immune responses for the lysis of malignant cells, modulation of the tumor microenvironment, and exertion of vaccine-like activities. However, efficient clinical exploitation of these potent therapeutic modules requires their systematic administration, especially against metastatic and solid tumors. Therefore, developing methods for shielding a virus from the neutralizing environment of the bloodstream while departing toward tumor sites is a must. This paper reports the latest advancements in the employment of chemical and biological compounds aimed at safe and efficient delivery of OVs to target tissues or tumor deposits within the host.

Synergistic Therapeutic Effects of Probiotic Lactobacillus casei TD-2 Consumption on GM-CSF-Induced Immune Responses in a Murine Model of Cervical Cancer.

We perceive the potential of combined immunotherapy for the synergistic treatment of human papillomavirus (HPV)-associated tumors. So, the tumor inhibiting effects of combination of L. casei TD2a and GM-CSF on the TC-1 growth were evaluated In Vivo using lymphocyte proliferation, lymphocyte cytotoxicity, splenocyte, and tumor cytokine assays. The results showed that tumor inhibition in transplanted mice in the GM-CSF combined with probiotic L. casei group was significantly higher than that observed in the other groups excluding GM-CSF group whose tumor inhibition effect was considerable. The findings also indicated that the combined group could generate tumor-specific cytolytic and splenocyte proliferative responses. The levels of IFN-γ, IL-4, and IL-12 after treating with GM-CSF combined with probiotic L. casei were significantly higher than those of other groups. The intratumoral Tumor Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL) was also significantly increased in the combined group. Tumor analysis further showed that the combined group decreased the accumulation of IL-10 in the tumor microenvironment of treated mice. Furthermore, tumor volume analysis demonstrated that combination group and even GM-CSF suppress tumor growth. Our findings showed that the combination of GM-CSF and probiotic results in improved tumor suppression against HPV-associated tumors and stimulates enhancement of specific antitumor immune responses.

Spectrum of lymphoma subtypes based on the latest World Health Organization classification in southern Iran from 2000 to 2011.

Background: Lymphoma, both Hodgkin and non-Hodgkin, is one of the most common malignancies, with a distinct subtype distribution throughout the world. Methods: A total of 453 lymphoma cases, identified retrospectively from January 2000 to October 2011, were studied to identify the subtype distribution of lymphoma in our center, located in southern Iran, according to the latest WHO classification. Results: The most common sites of involvement of all lymphomas were extranodal (59.16%). The highest frequency of extranodal sites in all lymphoid neoplasms were associated with diffuse large B-cell lymphoma (22.95%) and classical Hodgkin lymphoma (10.15%). Of 453 cases, 23 (5.32%) were T and natural killer cell neoplasms, of which the most common subtypes were T-cell large granular lymphocytic leukemia and anaplastic large cell lymphoma. Conclusion: This study indicated that the subtype distribution of lymphoma (except for the higher prevalence of diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma and lower rate of follicular lymphoma) in this part of Iran is similar to that in the Middle Eastern countries. Mature B-cell neoplasms are less frequent compared with both western and far east Asian countries.

A bibliometric review of oncolytic virus research as a novel approach for cancer therapy.

BACKGROUND: In recent years, oncolytic viruses (OVs) have drawn attention as a novel therapy to various types of cancers, both in clinical and preclinical cancer studies all around the world. Consequently, researchers have been actively working on enhancing cancer therapy since the early twentieth century. This study presents a systematic review of the literature on OVs, discusses underlying research clusters and, presents future directions of OVs research. METHODS: A total of 1626 published articles related to OVs as cancer therapy were obtained from the Web of Science (WoS) database published between January 2000 and March 2020. Various aspects of OVs research, including the countries/territories, institutions, journals, authors, citations, research areas, and content analysis to find trending and emerging topics, were analysed using the bibliometrix package in the R-software. RESULTS: In terms of the number of publications, the USA based researchers were the most productive (n = 611) followed by Chinese (n = 197), and Canadian (n = 153) researchers. The Molecular Therapy journal ranked first both in terms of the number of publications (n = 133) and local citations (n = 1384). The most prominent institution was Mayo Clinic from the USA (n = 117) followed by the University of Ottawa from Canada (n = 72), and the University of Helsinki from Finland (n = 63). The most impactful author was Bell J.C with the highest number of articles (n = 67) and total local citations (n = 885). The most impactful article was published in the Cell journal. In addition, the latest OVs research mainly builds on four research clusters. CONCLUSION: The domain of OVs research has increased at a rapid rate from 2000 to 2020. Based on the synthesis of reviewed studies, adenovirus, herpes simplex virus, reovirus, and Newcastle disease virus have shown potent anti-cancer activity. Developed countries such as the USA, Canada, the UK, and Finland were the most productive, hence, contributed most to this field. Further collaboration will help improve the clinical research translation of this therapy and bring benefits to cancer patients worldwide.

Protective cellular and mucosal immune responses following nasal administration of a whole gamma-irradiated influenza A (subtype H1N1) vaccine adjuvanted with interleukin-28B in a mouse model.

The use of gamma-irradiated influenza A virus (γ-Flu), retains most of the viral structural antigens, represent a promising option for vaccine development. However, despite the high effectiveness of γ-Flu vaccines, the need to incorporate an adjuvant to improve vaccine-mediated protection seems inevitable. Here, we examined the protective efficacy of an intranasal gamma-irradiated HIN1 vaccine co-administered with a plasmid encoding mouse interleukin-28B (mIL-28B) as a novel adjuvant in BALB/c mice. Animals were immunized intranasally three times at one-week intervals with γ-Flu, alone or in combination with the mIL-28B adjuvant, followed by viral challenge with a high lethal dose (10 LD50) of A/PR/8/34 (H1N1) influenza virus. Virus-specific antibody, cellular and mucosal responses, and the balance of cytokines in the spleen IFN-γ, IL-12, and IL-4) and in lung homogenates (IL-6 and IL-10) were measured by ELISA. The lymphoproliferative activity of restimulated spleen cells was also determined by MTT assay. Furthermore, virus production in the lungs of infected mice was estimated using the Madin-Darby canine kidney (MDCK)/hemagglutination assay (HA). Our data showed that intranasal immunization with adjuvanted γ-Flu vaccine efficiently promoted humoral, cellular, and mucosal immune responses and efficiently decreased lung virus titers, all of which are associated with protection against challenge. This combination also reduced IL-6 and IL-10 levels in lung homogenates. The results suggest that IL-28B can enhance the ability of the vaccine to elicit virus-specific immune responses and could potentially be used as an effective adjuvant.

Correction to: Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment.

An amendment to this paper has been published and can be accessed via the original article.

Correction to: CRISPR-Cas, a robust gene-editing technology in the era of modern cancer immunotherapy.

[This corrects the article DOI: 10.1186/s12935-020-01546-8.].

Correction to: Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade.

[This corrects the article DOI: 10.1186/s12935-020-01476-5.].

Correction to: Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?

[This corrects the article DOI: 10.1186/s12935-020-01219-6.].

CRISPR-Cas, a robust gene-editing technology in the era of modern cancer immunotherapy.

Cancer immunotherapy has been emerged as a promising strategy for treatment of a broad spectrum of malignancies ranging from hematological to solid tumors. One of the principal approaches of cancer immunotherapy is transfer of natural or engineered tumor-specific T-cells into patients, a so called "adoptive cell transfer", or ACT, process. Construction of allogeneic T-cells is dependent on the employment of a gene-editing tool to modify donor-extracted T-cells and prepare them to specifically act against tumor cells with enhanced function and durability and least side-effects. In this context, CRISPR technology can be used to produce universal T-cells, equipped with recombinant T cell receptor (TCR) or chimeric antigen receptor (CAR), through multiplex genome engineering using Cas nucleases. The robust potential of CRISPR-Cas in preparing the building blocks of ACT immunotherapy has broaden the application of such therapies and some of them have gotten FDA approvals. Here, we have collected the last investigations in the field of immuno-oncology conducted in partnership with CRISPR technology. In addition, studies that have addressed the challenges in the path of CRISPR-mediated cancer immunotherapy, as well as pre-treatment applications of CRISPR-Cas have been mentioned in detail.

Synergy between hemagglutinin 2 (HA2) subunit of influenza fusogenic membrane glycoprotein and oncolytic Newcastle disease virus suppressed tumor growth and further enhanced by Immune checkpoint PD-1 blockade.

BACKGROUND: Newcastle disease virus (NDV) has shown noticeable oncolytic properties, especially against cervical cancer. However, in order to improve the spread rate and oncotoxicity of the virus, employment of other therapeutic reagents would be helpful. It has been shown that some viral fusogenic membrane glycoproteins (FMGs) could facilitate viral propagation and increase the infection rate of tumor cells by oncolytic viruses. Additionally, immune checkpoint blockade has widely been investigated for its anti-tumor effects against several types of cancers. Here, we investigated for the first time whether the incorporation of influenza hemagglutinin-2 (HA2) FMG could improve the oncolytic characteristics of NDV against cervical cancer. Next, we added anti-PD-1 mAb to our therapeutic recipe to assess the complementary role of immune checkpoint blockade in curbing tumor progression. METHODS: For this purpose, TC-1 tumor cells were injected into the mice models and treatment with NDV, iNDV, HA2, NDV-HA2, iNDV-HA2 began 10 days after tumor challenge and was repeated at day 17. In addition, PD-1 blockade was conducted by injection of anti-PD-1 mAb at days 9 and 16. Two weeks after the last treatment, sample mice were sacrificed and treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, tumors condition was monitored weekly for 6 weeks intervals and the tumor volume was measured and compared within different groups. RESULTS: The results of co-treatment with NDV and HA2 gene revealed that these agents act synergistically to induce antitumor immune responses against HPV-associated carcinoma by enhancement of E7-specific lymphocyte proliferation, inducement of CD8+ T cell cytotoxicity responses, increase in splenic cytokines and granzyme B, decrease in immunosuppressive cytokines and E6 oncogene expression, and upregulation of apoptotic proteins expression, in comparison with control groups. Moreover, incorporation of PD-1 blockade as the third side of our suggested therapy led to noticeable regression in tumor size and augmentation of cytokine responses. CONCLUSIONS: The invaluable results of synergy between NDV virotherapy and HA2 gene therapy suggest that tumor-selective cell killing by oncolytic NDV can be enhanced by combining with FMG gene therapy. Moreover, the adjunction of the PD-1 blockade proves that checkpoint blockade can be considered as an effective complementary therapy for the treatment of cervical cancer.

Oncolytic effects of Hitchner B1 strain of newcastle disease virus against cervical cancer cell proliferation is mediated by the increased expression of cytochrome C, autophagy and apoptotic pathways.

Newcastle disease virus (NDV) is a potential oncolytic virus for the cancer treatment due to its ability to replicate in tumor cells. The aim of this study was to evaluate the in vitro anticancer properties of Hitchner B1 (HB1) strain of NDV on TC-1 cell line and underlying molecular mechanisms. The cytolytic effects of oncolytic HB1 strain of NDV was determined by lactate dehydrogenase (LDH) release assay. Apoptosis, intracellular reactive oxygen species (ROS) levels, cleaved caspase-3 and autophagy were evaluated by flow cytometry. Cytochrome-C and survivin protein levels were distinguished by Enzyme-Linked Immunosorbent Assay (ELISA). Our results from LDH method showed that the viability of the TC-1 cell line following HB1 NDV infection was dose-dependent and decreased significantly with increasing the dose of HB1 NDV infection (MOIs: 5, 10, and 15). Other evaluations also revealed that HB1 strain of NDV potentially led to the ROS production, and apoptosis and autophagy induction in TC-1 cell line in a dose-dependent manner. The in vitro experiments also presented that NDV treatment significantly up-regulated the expression of cytochrome-C and down-regulated the expression of survivin, as detected by ELISA assay. Our results confirmed that the HB1 NDV could be introduced as a powerful candidate for the therapy of cervical cancer. However, further examinations are needed to explain the underlying mechanisms of the HB1 NDV against TC-1 cell line and cervical cancer.

Evaluation of Inflammatory State in Migraineurs: A Case-control Study.

Due to inconclusive findings of previous researches, we aimed to evaluate inflammatory state biomarkers in episodic and chronic migraineurs (EM and CM patients) compared to headache-free controls in the current study. Seventy-one migraine patients and 19 age-sex-matched controls were recruited. After obtaining demographic data and recording headache characteristics, blood samples were gathered and analyzed to evaluate the serum levels of C-reactive protein (CRP), tumor necrosis factor(TNF)-α and interleukin (IL)-6. Serum levels of IL-6, CRP and TNF-α were significantly higher among subjects with CM than the EM and controls. Further, positive correlations were noted for number of headache days/month and serum IL-6 (r=0.53, p<0.001), CRP (r=0.62, p<0.001), and TNF-α (r=0.58, p<0.001). In sum, according to current findings, a pro-inflammatory state was detected among chronic and episodic migraineurs compared to healthy control, as revealed by augmented concentrations of pro-inflammatory cytokines (e.g. IL6, CRP, and TNF-α). It was also underlined that with increasing levels of inflammatory factors, headaches tended to be more chronic. However, in order to confirm the hypothesis that neuroinflammation plays a role in migraine pain genesis, long-term cohort studies and well-designed experimental and randomized controlled trials are required.

Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment.

BACKGROUND: Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor. METHODS: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune responses, caspase-3 and -9 expression, and myeloid and myeloid-derived suppressor cells (MDSCs) by histological and immunohistochemical studies in the tumor microenvironment (TME). RESULTS: Our findings proved that MSCs possess both migratory capacity and tumor tropism toward transplanted tumor tissue after peritumoral administration. Tumor therapy experiments indicated that oncolytic NDV delivered by MSCs-engineered system significantly reduces tumor growth, which is associated with the enhancement of E7-specific lymphocyte proliferation, CD8+ T cell cytolysis responses, and splenic IFN-γ, IL-4 and IL-12 responses compared with control groups. Moreover, the treatment upregulated the concentration of apoptotic proteins (caspase 9) and increased infiltration of tumor microenvironment with CD11b + myeloid and Gr1 + MDSCs cells. CONCLUSIONS: Our data suggest MSCs carrying oncolytic NDV as a potentially effective strategy for cancer immunotherapy through inducing splenic Th1 immune responses and apoptosis in the tumor microenvironment.