oncolytic viruses pathway

Oncolytic virotherapy stands out as a burgeoning and promising therapeutic paradigm, harnessing the intrinsic cytotoxicity of oncolytic viruses for selective replication and dissemination within tumors. The primary mode of action revolves around the direct eradication of tumor cells. In our previous investigations, we formulated an oncolytic herpes simplex virus type 2 (OH2) and substantiated its anti-tumor efficacy both in vivo and in vitro. Subsequently, we embarked on a phase I/II clinical trial in China (NMPA, 2018L02743) and the USA (FDA, IND 27137) to assess OH2's safety, biodistribution, and anti-tumor activity as a standalone agent in patients with advanced solid tumors...

BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) is a common type of cancer that has a high death rate and is becoming more common in developed countries. Currently, there are several treatment options available for CRC patients, and clinical trials are being conducted to improve conventional therapies. This study investigates the combined impact of Bacillus coagulans (B.C) and Newcastle disease virus (NDV) on the growth of human colorectal adenocarcinoma cells (HT29 cell line). MATERIALS AND METHODS: The HT29 cell line was cultured under controlled laboratory conditions...

Stimulator of interferon genes (STING)-dependent signaling is requisite for effective anti-microbial and anti-tumor activity. STING signaling is commonly defective in cancer cells, which enables tumor cells to evade the immunosurveillance system. We evaluate here whether intrinsic STING signaling in such tumor cells could be reconstituted by creating recombinant herpes simplex viruses (rHSVs) that express components of the STING signaling pathway. We observe that rHSVs expressing STING and/or cGAS replicate inefficiently yet retain in vivo anti-tumor activity, independent of oncolytic activityrequisite on the trans-activation of extrinsic STING signaling in phagocytes by engulfed microbial dsDNA species...

Glioblastoma is most commonly a primary brain tumor and the utmost malignant one, with a survival rate of approximately 12-18 months. Glioblastoma is highly heterogeneous, demonstrating that different types of cells from the same tumor can manifest distinct gene expression patterns and biological behaviors. Conventional therapies such as temozolomide, radiation, and surgery have limitations. As of now, there is no cure for glioblastoma. Alternative treatment methods to eradicate glioblastoma are discussed in this review, including targeted therapies to PI3K, NFKβ, JAK-STAT, CK2, WNT, NOTCH, Hedgehog, and TGFβ pathways...

Malignant ascites is a common complication resulting from the peritoneal spread of malignancies, and currently lacks effective treatments. We conducted a phase II trial (NCT04771676) to investigate the efficacy and safety of oncolytic adenovirus H101 and virotherapy-induced immune response in 25 patients with malignant ascites. Oncolytic virotherapy achieved an increased median time to repeat paracentesis of 45 days (95% confidence interval 16.5-73.5 days), compared to the preset control value of 13 days. Therapy was well-tolerated, with pyrexia, fatigue, nausea, and abdominal pain as the most common toxicities...

Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of metastatic or recurrent sarcoma remains poor. The current study presents two cases of sarcoma enrolled in a phase I dose escalation trial for solid tumor, who had previously failed all standard therapies. These patients were treated with VG161, an immune-stimulating herpes simplex virus type 1 oncolytic virus with payloads of IL-12, IL-15 and IL-15 receptor α unit, and a programmed cell death 1 (PD-1)/PD-1 ligand 1 blocking peptide...

BACKGROUND: Colorectal Cancer (CRC) represents a significant global health challenge, and its progression, resistance to therapy, and metastasis are strongly influenced by the tumor microenvironment, including factors like hypoxia. This study explores the impact of High Mobility Group Box 1 (HMGB1) overexpression on CRC cell migration, while identifying potential genes associated with this process. METHODS: To explore this, we developed oncolytic virotherapy, resulting in HSVHMGB1, an oncolytic Herpes simplex virus that expresses HMGB1...

Identifying potential cancer-associated genes and drug targets from omics data is challenging due to its diverse sources and analyses, requiring advanced skills and large amounts of time. To facilitate such analysis, we developed Cat-E ( Ca ncer T arget E xplorer), a novel R/Shiny web tool designed for comprehensive analysis with evaluation according to cancer-related omics data. Cat-E is accessible at https://cat-e.bioinfo-wuerz.eu/. Cat-E compiles information on oncolytic viruses, cell lines, gene markers, and clinical studies by integrating molecular datasets from key databases such as OvirusTB, TCGA, DrugBANK, and PubChem...

Despite recent advancements in the diagnosis and treatment of breast cancer (BC), patient outcomes in terms of survival, recurrence, and disease progression remain suboptimal. A significant factor contributing to these challenges is the cellular heterogeneity within BC, particularly the presence of breast cancer stem cells (BCSCs). These cells are thought to serve as the clonogenic nexus for new tumor growth, owing to their hierarchical organization within the tumor. This descriptive review focuses on the evolving strategies to target BCSCs, which have become a pivotal aspect of therapeutic development...

Ferroptosis, a necrotic, iron-dependent controlled cell death mechanism, is distinguished by the development of lipid peroxides to fatal proportions. Malignant tumours, influenced by iron to promote fast development, are vulnerable to ferroptosis. Based upon mounting evidence it has been observed that ferroptosis may be immunogenic and hence may complement immunotherapies. A new approach includes iron oxide-loaded nano-vaccines (IONVs), having supremacy for the traits of the tumour microenvironment (TME) to deliver specific antigens through improving the immunostimulatory capacity by molecular disintegration and reversible covalent bonds that target the tumour cells and induce ferroptosis...

Colorectal cancer (CRC) is a frequent gastrointestinal malignancy with high rates of morbidity and mortality; 85% of these tumours are proficient mismatch repair (pMMR)-microsatellite instability-low (MSI-L)/microsatellite stable (MSS) CRC known as 'cold' tumours that are resistant to immunosuppressive drugs. Monotherapy with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors is ineffective for treating MSS CRC, making immunotherapy for MSS CRC a bottleneck. Recent studies have found that the multi-pathway regimens combined with PD-1/PD-L1 inhibitors can enhance the efficacy of anti-PD-1/PD-L1 in MSS CRC by increasing the number of CD8+ T cells, upregulating PD-L1 expression and improving the tumour microenvironment...

Immunostimulatory gene therapy using oncolytic viruses is currently evaluated as a promising therapy for cancer aiming to induce anti-tumour immunity. Here, we investigate the capacity of oncolytic adenoviruses (LOAd) and their transgenes to induce immunogenicity in the infected tumour cells. Oncolysis and death-related markers were assessed after infection of eight human solid cancer cell lines with different LOAd viruses expressing a trimerized, membrane-bound (TMZ)-CD40L, TMZ-CD40L and 41BBL, or no transgenes...

Human Adenoviruses (HAdV) are nearly ubiquitous pathogens comprising numerous sub-types that infect various tissues and organs. Among many encoded proteins that facilitate viral replication and subversion of host cellular processes, the viral E4orf1 protein has emerged as an intriguing yet under-investigated player in the complex interplay between the virus and its host. E4orf1 has gained attention as a metabolism activator and oncogenic agent, while recent research is showing that E4orf1 may play a more important role in modulating cellular pathways such as PI3K-Akt-mTOR, Ras, the immune response and further HAdV replication stages than previously anticipated...

Ferroptosis, a form of programmed cell death characterized by iron-dependent lipid peroxidation, has recently gained considerable attention in the field of cancer therapy. There is significant crosstalk between ferroptosis and several classical signaling pathways, such as the Hippo pathway, which suppresses abnormal growth and is frequently aberrant in tumor tissues. Yes-associated protein 1 (YAP), the core effector molecule of the Hippo pathway, is abnormally expressed and activated in a variety of malignant tumor tissues...

Oncolytic viruses (OVs) can selectively replicate in tumor cells and remodel the microenvironment of immunologically cold tumors, making them a promising strategy to evoke antitumor immunity. Similarly, agonists of the stimulator of interferon genes (STING)-interferon (IFN) pathway, the main cellular antiviral system, provide antitumor benefits by inducing the activation of dendritic cells (DC). Considering how the activation of the STING-IFN pathway could potentially inhibit OV replication, the use of STING agonists alongside OV therapy remains largely unexplored...

Oncolytic viruses (OVs) are appealing anti-tumor agents. But it is limited in its effectiveness. In this study, we used combination therapy with immune checkpoint inhibitor to enhance the antitumor efficacy of OVs. Using reverse genetics technology, we rescued an oncolytic influenza virus with the name delNS1-GM-CSF from the virus. After identifying the hemagglutination and 50% tissue culture infectivedose (TCID50 ) of delNS1-GM-CSF, it was purified, and the viral morphology was observed under electron microscopy...

BACKGROUND: Due to the existence of tumor stem cells with tumorigenicity properties and resistance patterns, treatment of glioblastoma is not easy. Hypoxia is a major concern in glioblastoma therapy. Telomerase activity and telomere length alterations have been known to play a critical role in glioblastoma progression and invasion. OBJECTIVE: This study aimed to investigate the effects of HSV-G47Δ oncolytic virus on telomerase and telomere length alterations in U251GBMCSCs (U251-Glioblastoma cancer stem cells) under hypoxia and normoxia conditions...

The measles vaccine virus strain (MV-Edm) serves as a potential platform for the development of effective oncolytic vectors. Nevertheless, despite promising pre-clinical data, our comprehension of the factors influencing the efficacy of MV-Edm infection and intratumoral spread, as well as the interactions between oncolytic viruses and specific chemotherapeutics associated with viral infection, remains limited. Therefore, we investigated the potency of Forskolin in enhancing the antitumor effect of oncolytic MV-Edm by promoting the Rab27a-dependent vesicular transport system...

There have been many recent advances in melanoma therapy. While 50% of melanomas have a BRAF mutation and are a target for BRAF inhibitors, the remaining 50% are BRAF wild-type. Immune checkpoint inhibitors targeting PD-1, cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and lymphocyte activated gene-3 (Lag-3) are all approved for the treatment of patients with advanced BRAF wild-type melanoma; however, treatment of this patient population following initial immune checkpoint blockade is a current therapeutic challenge given the lack of other efficacious options...

Targeting actionable mutations in oncogene-driven cancers and the evolution of immuno-oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity...