Clinical Trials Logo

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of novel oncolytic virus in late stage solid tumors.


Clinical Trial Description

Oncolytic viruses (OVs) are naturally occurring or recombinant viruses that can selectively destroy tumor cells without harming normal cells. After infecting the host, oncolytic viruses can replicate within host cells, and the progeny viruses released can further infect neighboring host cells and kill the tumor while triggering local or systemic anti-tumor immune responses. Compared to traditional treatments, oncolytic virus therapy offers advantages such as good targeting, minimal adverse reactions, multiple tumor-killing pathways, and reduced likelihood of developing resistance. Several clinical studies have found that oncolytic viruses can provide clinical benefits to patients with different types, stages, and even advanced metastatic tumors. Importantly, when used in combination with radiation therapy or chemotherapy, they exhibit good synergistic effects. Especially when used in combination with immunotherapy, oncolytic viruses can sensitize tumor types that were initially unresponsive to immune checkpoint inhibitors. Currently, oncolytic viruses are believed to exert anti-tumor activity through three main mechanisms: 1. Direct Oncolytic Effect: Oncolytic viruses can undergo specific replication within tumor cells, primarily due to the tumor's specific genetic alterations that prevent the cell's signaling pathways from sensing and blocking virus replication. Tumor interferon defects prevent the regulation of the virus defense system, increasing sensitivity to virus infection. By genetic modification, the virulence factors of oncolytic viruses can be weakened or deleted, preventing virus replication in normal tissues while retaining the ability to replicate within tumor cells and kill them. 2. Elicitation of Anti-Tumor Immune Responses: Oncolytic virus infection of tumor cells can transform "cold" tumors into "hot" tumors, thereby triggering local and systemic anti-tumor immune responses. Immune suppressive factors in the tumor microenvironment, such as regulatory lymphocytes, interleukin-10 (IL-10), and programmed death-ligand 1 (PD-L1), can protect tumors from immune surveillance. Oncolytic viruses disrupt the existing tissue structure in the tumor microenvironment and can reverse the immunosuppressive microenvironment, transitioning it from immune suppression to immune activation. After oncolytic virus infection of tumor cells, cell lysis occurs, releasing tumor-associated antigens, activating dendritic cells, increasing the infiltration of cytotoxic T lymphocytes, and recruiting other immune-related cells and molecules. This results in an increase in tumor-specific immune responses, leading to the clearance of distant and uninfected tumor cells. 3. Expression of Anti-Tumor Target Genes and Anti-Angiogenesis: Through genetic engineering, oncolytic viruses can express target genes that have anti-tumor effects, such as P53, GM-CSF, IL-12, IL-15, anti-PD-L1, etc., further enhancing their anti-tumor effects. In addition, some oncolytic viruses can infect and destroy the tumor's vascular system, inducing neutrophil infiltration, leading to vascular collapse and tumor cell death. Oncolytic viruses (OVs) can be categorized into DNA virus carriers and RNA virus carriers based on the type of nucleic acid in their genomes. DNA viruses mainly include herpes simplex virus (HSV), adenovirus (AdV), vaccinia virus (VV), and parvovirus H1; while RNA viruses mainly include reovirus (RV), Coxsackievirus (CV), poliovirus (PV), measles virus (MV), Newcastle disease virus (NDV), and vesicular stomatitis virus (VSV). Among them, the five most commonly used oncolytic viruses in clinical research are adenovirus, HSV-1, reovirus, vaccinia virus, and Newcastle disease virus. To date, five oncolytic virus products have been approved for marketing globally. There are hundreds of projects in clinical trial stages, especially in recent years, new generations of oncolytic viruses developed and marketed or in clinical stages have shown better safety and stronger anti-tumor capabilities. Our project team has isolated and modified multiple strains of genetically engineered oncolytic herpes viruses, selecting the best strains for in vivo and in vitro pharmacological and safety evaluations. We have achieved anti-tumor effects superior to currently approved oncolytic virus control drugs. This virus has been engineered to delete virulence factors that are toxic to normal cells, and genetic engineering modifications have been made at multiple genomic loci. It can selectively replicate in tumor cells and can express recombinant bispecific antibodies at high levels. Compared to existing oncolytic virus formulations, this virus demonstrates improved safety and anti-tumor activity and holds great promise for clinical translation. In preliminary studies, the project team has also demonstrated significant anti-tumor effects of oncolytic adenovirus expressing this bispecific antibody. Therefore, in this clinical trial, our project team plans to conduct clinical translational research using the original strain based on proprietary intellectual property that has undergone genetic engineering improvements. The implementation of this project will provide a highly potential and hopeful clinical treatment strategy for advanced cancer patients with no other treatment options. It will also provide new ideas, strategies, and experimental evidence for the development of oncolytic virus new drugs. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT06080984
Study type Interventional
Source West China Hospital
Contact Xingchen Peng
Phone +86 18980606753
Email pxx2014@163.com
Status Recruiting
Phase Phase 1
Start date October 15, 2023
Completion date October 15, 2025

See also
  Status Clinical Trial Phase
Recruiting NCT04691349 - CAR-T for r/r Malignant Tumors in Children Early Phase 1
Recruiting NCT04672473 - Treatment of Malignant Tumors With Antigen Peptide-specific DC-CTL Cells and Decitabine Phase 1/Phase 2
Recruiting NCT04991506 - A Study of ES102 (OX40 Agonist) in Combination With JS001 in Patients With Advanced Solid Tumors Phase 1
Completed NCT02552004 - Assessment of Intraoperative Probe-based Confocal Laser Endomicroscopy in Digestive and Endocrine Surgery: a Pilot Study N/A
Recruiting NCT05280873 - Pirfenidone Combined With Methylprednisolone Versus Methylprednisolone in the Treatment of CIP Phase 1
Completed NCT06093945 - Effect of Omeprazole on Pharmacokinetics of SHR2554 in Healthy Subjects Phase 1
Completed NCT05592262 - Pharmacokinetic Test of High-fat Diet After Oral Administration of SHR2554 in Healthy Subjects Phase 1
Completed NCT03012945 - Epidural Anesthesia-analgesia and Long-term Outcome N/A
Recruiting NCT04686682 - A First-in-Human, JAB-8263 in Adult Patients With Advanced Tumors Phase 1/Phase 2
Recruiting NCT06084767 - 68Ga-TCR-FAPI PET/CT in Patients With Various Types of Cancer N/A
Enrolling by invitation NCT02937246 - Efficacy of Partial Covered Double Bare Metal Stent Compared to Uncovered Double Bare Metal Stent in Malignant Biliary Obstruction N/A
Completed NCT03354741 - Stimulation of Acupuncture Points by Athermic Laser Therapy for the Prevention of Chemotherapy Induced Nausea and Vomiting in Children N/A
Recruiting NCT03931720 - Clinical Research of ROBO1 Specific BiCAR-NK/T Cells on Patients With Malignant Tumor Phase 1/Phase 2
Completed NCT01906632 - Gene Expression Profiling of Malignant Tumor Predict the Therapeutic Response of DC-CIK Immunotherapy N/A
Recruiting NCT05596344 - Long-term Follow-up of Anxiety and Depression in Patients With Malignant Tumors
Active, not recruiting NCT04230200 - Prospective Screening Programme for Malignant Tumors
Completed NCT04730843 - A Study of ES102 (OX40 Agonist) in Patients With Advanced Solid Tumors Phase 1
Completed NCT04952766 - Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults Phase 4
Recruiting NCT05781555 - A Study of Diffusing Alpha Radiation Therapy for Target Treatments of Malignant Tumors N/A
Completed NCT01884168 - Study of Gene Expression Profiling and Immunological Mechanism Affects the Response of Immunotherapy