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Systemic delivery of glycosylated-PEG-masked oncolytic virus enhances targeting of antitumor immuno-virotherapy and modulates T and NK cell infiltration.

Rationale: Immuno-virotherapy has emerged as a promising approach for cancer treatment, as it directly and cytotoxically eliminates tumors with systemic immune stimulation. However, the clinical efficacy of this approach remains limited by inappropriate delivery routes, robust antiviral responses, and the tumor immunosuppressive microenvironment. Methods: To address these challenges, we propose a surface engineering strategy that masks oncolytic herpes simplex virus (oHSV) with a galactose-polyethylene-glycol (PEG) polymer chain to minimize host antiviral responses and selectively targets tumo

Enhanced Sensitivity of Patient-Derived Pediatric High-Grade Brain Tumor Xenografts to Oncolytic HSV-1 Virotherapy Correlates with Nectin-1 Expression.

Pediatric high-grade brain tumors and adult glioblastoma are associated with significant morbidity and mortality. Oncolytic herpes simplex virus-1 (oHSV) is a promising approach to target brain tumors; oHSV G207 and M032 (encodes human interleukin-12) are currently in phase I clinical trials in children with malignant supratentorial brain tumors and adults with glioblastoma, respectively. We sought to compare the sensitivity of patient-derived pediatric malignant brain tumor and adult glioblastoma xenografts to these clinically-relevant oHSV. In so doing we found that pediatric brain tumors we

Интеграция многомерного согласованного сайта СТАТ в аденовальный геном для вмешательства в сигнализацию IFN представляет собой новую концепцию совершенствования онколитической виротерапии.

Аденовирусная инфекция вызывает интерферонную реакцию (IFN), которая уменьшает тиражирование вирусного генома в начале аденовального жизненного цикла. В онколитической терапии вирусное воспроизведение необходимо для эффективного клеточного лиза, который впоследствии может активировать системную иммунную реакцию на опухоль. Мы показываем, что различные члены семейства белков JAK/STAT чрезмерно способствуют подавлению аденовального копирования в раковых клетках мочевого пузыря. Этот механизм требует выражения Е1А; однако он влияет не на уровни выражения Е1А, а скорее на его трансактивацию E1B55K

Совпадение в аннотации оригинала
Adenovirus infection triggers an interferon (IFN) response that reduces replication of the viral genome early in the adenoviral life cycle. … systemic immune response but also cause serious adverse effects.IMPORTANCESuccessful application of oncolytic virotherapy requires efficient virus replication that can be suppressed by the host's cell antiviral IFN response. We extend in this study the insight into the underlying molecular mechanisms in bladder cancer cells. Suppression of JAK/STAT activity induces an …

Comparative safety and efficacy of oncolytic virotherapy for the treatment of individuals with malignancies: a systematic review, meta-analysis, and Bayesian network meta-analysis.

BACKGROUND: Oncolytic virotherapy (OV) is an innovative immunotherapy strategy. A comprehensive understanding of oncolytic viruses is essential for advancing research and clinical practice. This analysis aims to evaluate the clinical outcomes of oncolytic virotherapy in cancer patients. METHODS: We performed single-arm, pairwise, and Bayesian network meta-analyses, incorporating clinical trials identified through PubMed, Medline, Embase, and the Cochrane Library from database inception to April 30, 2025. Primary endpoints included all-grade and grade ≥3 adverse events (AEs), objective respons…

The practical self-targeted oncolytic adenoviral nanosphere based on immuno-obstruction method via polyprotein surface precipitation technique enhances transfection efficiency for virotherapy.

Recent developments in tumour treatment had focused on virotherapies that were currently revolutionising new innovated treatment pathways. This study focused on the fabrication of oncolytic adenoviral vector (Ad) nanosphere that self-targeted at lung tumour cells (A549), utilising the immune response for upper respiratory tract infection, caused by the Ad infection. This system was dependent upon T-cell immune response, surface charge and blood metabolism. Oncolytic Ad attacked lung A549 tumour cells by incorporated its own DNA to replace A549's, the triggered immune response generated T-cells

Prophylactic alpha interferon treatment increases the therapeutic index of oncolytic vesicular stomatitis virus virotherapy for advanced hepatocellular carcinoma in immune-competent rats.

Vesicular stomatitis virus (VSV) is a negative-strand RNA virus with intrinsic oncolytic specificity due to substantially attenuated antivir … lactic application should be considered in future clinical translational protocols for VSV-mediated oncolytic virotherapy as a novel therapeutic modality in patients with advanced HCC, as well as other types of cancer.

The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach.

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, …

An armed, YB-1-dependent oncolytic adenovirus as a candidate for a combinatorial anti-glioma approach of virotherapy, suicide gene therapy and chemotherapeutic treatment.

We investigated the novel recombinant oncolytic adenovirus Ad-delo-sr39TK-RGD, armed with a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39TK) as a suicide gene, and explored its antitumor efficacy in combination with HSV1-sr39TK/ganciclovir (GCV) gene therapy and temozolomide (TMZ). Ad-delo-sr39TK-RGD is an E1-mutated conditionally replicating adenovirus dependent on the human Y-box binding protein 1 (YB-1). Thus, we utilized the YB-1 dependency of the vector to target human glioma cells in vitro, using two-dimensional cell culture and three-dimensional multicellular spheroids,

Enhancing oncolytic virotherapy with a tri-specific T-cell engager targeting CD3ε, EpCaM, and 4-1BB: preclinical evaluation and implications for cancer immunotherapy.

BACKGROUND: Cytotoxic T-cell-mediated tumor lysis is a key mechanism of oncolytic virotherapy. While oncolytic viruses expressing bispecific T-cell engagers (BiTE) enhance tumor targeting, they lack costimulatory signals, leading to T-cell exhaustion. We developed an oncolytic adenovirus expressing a trispecific T-cell engager (TriTE) to improve antitumor responses in colorectal carcinoma models. METHODS: An oncolytic adenovirus (Ad5-TriTE) was engineered to express a TriTE molecule targeting EpCAM (tumor antigen), CD3ε (T-cell activation), and 4-1BB (co-stimulation). For comparison, a BiTE-e…

Whole-Transcriptome Profiling of Murine GL261 Glioma Reveals Signatures Consistent with Distinct Immune Reprogramming Induced by Oncolytic Virotherapy with VV-GMCSF-Lact and Anti-PD-1 Therapy.

Both oncolytic virotherapy and immune checkpoint blockade are being actively explored as immunotherapy treatments for glioblastoma, one of the most lethal malignancies. Nevertheless, the antitumor molecular mechanisms of these therapies remain poorly understood, particularly whether they induce overlapping or distinct transcriptional programs. No comprehensive transcriptome-wide characterization and direct comparison of the responses induced by VV-GMCSF-Lact and anti-PD-1 therapy in glioma have been reported. To address this question, we performed whole-transcriptome profiling of GL261 tumors …

Novel Oncolytic Herpes Simplex Virus 1 VC2 Promotes Long-Lasting, Systemic Anti-melanoma Tumor Immune Responses and Increased Survival in an Immunocompetent B16F10-Derived Mouse Melanoma Model.

Oncolytic virotherapy (OVT) is now understood to be an immunotherapy that uses viral infection to liberate tumor antigens in an immunogenic context to promote the development of antitumor immune responses. The only currently FDA-approved oncolytic virotherapy, T-Vec, is a modified type 1 herpes simplex virus (HSV-1). While T-Vec is associated with limited response rates, its modest efficacy supports the continued development of novel OVT viruses. Herein, we test the efficacy of a recombinant HSV-1, VC2, as an OVT in a syngeneic B16F10-derived mouse model of melanoma. VC2 possesses mutations th…

Macrophage response to oncolytic paramyxoviruses potentiates virus-mediated tumor cell killing.

Tumor-associated macrophages (TAMs) are known to regulate tumor response to many anti-cancer therapies, including oncolytic virotherapy. Oncolytic virotherapy employing oncolytic paramyxoviruses, such as attenuated measles (MeV) and mumps (MuV) viruses, has demonstrated therapeutic potential against various malignancies. However, the response of TAMs to oncolytic paramyxoviruses and the consequent effect on virotherapeutic efficacy remains to be characterized. Here, we demonstrate that the presence of human monocyte-derived macrophages (MDMs), irrespective of initial polarization state, enhanc…

Novel oncolytic viral therapies in patients with thoracic malignancies.

Oncolytic virotherapy is the use of replication-competent viruses to treat malignancies. The potential of oncolytic virotherapy as an approach to cancer therapy is based on historical evidence that certain viral infections can cause spontaneous remission of both hematologic and solid tumor malignancies. Oncolytic virotherapy may eliminate cancer cells through either direct oncolysis of infected tumor cells or indirect immune-mediated oncolysis of uninfected tumor cells. Recent advances in oncolytic virotherapy include the development of a wide variety of genetically attenuated RNA viruses with…

Ferroptosis enhances the therapeutic potential of oncolytic adenoviruses KD01 against cancer.

Oncolytic virotherapy has emerged as a promising strategy for cancer treatment by selectively targeting and lysing tumor cells. However, its efficacy is often limited in certain tumor types due to multiple factors. This study explores the combination of oncolytic adenoviruses with Erastin, a potent ferroptosis inducer, to enhance antitumor efficacy in oncolytic virus-insensitive cancer cell lines. In vitro experiments demonstrated that Erastin significantly increased the cytotoxicity of oncolytic virotherapy, leading to greater inhibition of cell proliferation and elevated rates of cell death …

Reversing resistance to immune checkpoint inhibitor by adding recombinant human adenovirus type 5 in a patient with small cell lung cancer with promoted immune infiltration: a case report.

Small cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis. Since immune checkpoint inhibitors (ICIs) have had significant benefits in SCLC, studying and overcoming the mechanisms of ICI resistance have become critical. Oncolytic virotherapy has been demonstrated to improve the efficacy of anti-PD-1 therapy by favorably changing the tumor microenvironment. This suggests the potential of oncolytic virotherapy to overcome ICI resistance in SCLC. Herein, we report a patient with extensive-stage SCLC who underwent previous chemotherapy and ICI therapy since its recurrence. Becau…

Emerging Oncolytic Viruses: Beyond Adenoviruses and Herpes Simplex Virus.

Oncolytic virotherapy represents an innovative therapeutic modality in oncology, exploiting the selective tropism of viruses to target and eradicate malignant cells. Unlike conventional cancer treatments such as chemotherapy and radiotherapy, oncolytic viruses (OVs) exhibit a dual mechanism of action: direct tumor cell lysis and potent immune activation. This approach transforms tumors into in situ vaccines, generating durable anti-tumor immune memory. The field has garnered substantial attention following the regulatory approval of talimogene laherparepvec (T-VEC), a genetically engineered he…

The role and mechanism of neutrophils in oncolytic virus therapy.

Oncolytic viruses (OVs) are a class of viruses capable of specifically infecting and killing tumor cells. They exert antitumor effects through direct lysis of tumor cells, activation of the immune system, and disruption of tumor vasculature. Neutrophils, which originate from the bone marrow, are the most abundant leukocytes in peripheral blood and the immune system and play a dual regulatory role in oncolytic virotherapy. In different TME, neutrophils can polarize into two phenotypes: N1 and N2. N1 neutrophils, owing to their chemotaxis and tumor-homing capabilities, can serve as delivery vehi…

Tropism and transduction of oncolytic adenovirus vectors in prostate cancer therapy.

Oncolytic adenovirus has been applied in cancer therapy because of several advantages such as cost-effective production, high transduction efficiency and low toxicity. Recent efforts have been focused on the modification of oncolytic adenovirus by encoding transgenes within the viral genome to efficiently and selectively replicate within cancer cells, destroy cancerous cells, induce tumor cell apoptosis, and stimulate the recruitment of immune cells to the tumor site. Nevertheless, there are still big challenges for translational research of oncolytic virotherapy in clinical cancer management.…

Oncolytic Replication of E1b-Deleted Adenoviruses.

Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads) are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially r…

Oncolytic viruses in brain cancer therapy: advances, challenges, and clinical trial outcomes.

Malignant intracranial tumors are a major cause of morbidity and mortality across age groups. To assess recent progress in glioblastoma (GBM) oncolytic virotherapy, literature was searched in PubMed and Google Scholar using the keywords glioblastoma, oncolytic virus, clinical trials, brain tumor, and oncolytic virotherapy resistance. Relevant studies published through 2024 were reviewed. Brain tumors vary in prevalence, but many have poor prognosis and low survival rates. Among available treatment approaches, oncolytic virotherapy has gained strong attention as a promising cancer therapy. Exis…