The Application of Novel Oncolytic Virus in Late Stage Solid Tumors

Malignant Tumor Clinical Trial

Official title: The Application of Novel Oncolytic Virus in Late Stage Solid Tumors

Status Recruiting

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. ;

Related Conditions & MeSH terms

• Malignant Tumor
• Neoplasms

• 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