Engineered Oncolytic Virus Strain for Solid Tumor Therapy

Figure 1. Modes of Action of Oncolytic Viruses.

 

In a groundbreaking development, a team of researchers have engineered a novel strain of the herpes simplex virus type 1 (HSV-1), OncoDelta (OncoD), designed to target and destroy solid tumors while boosting the immune response against cancer. The study, led by Dr. Balveen Kaur and her team at Augusta University, was published in Molecular Therapy: Oncology and highlights the creation of a triple-mutated oncolytic virus highlights the potential of OncoD as a promising virotherapy for various cancer types, particularly in combination with radiation therapy.

“Oncolytic viruses have immense potential in cancer therapy, but improving their selectivity and efficacy has been a major challenge. Our work with OncoD shows that we can enhance tumor specificity while maintaining strong anti-tumor activity,” – said Dr. Balveen Kaur, senior author and professor at the Georgia Cancer Center at Augusta University.

A Breakthrough in Oncolytic Virotherapy

Oncolytic viruses are an emerging class of biotherapeutics that selectively infect and lyse cancer cells while stimulating immune responses against tumors, making them a powerful tool in cancer therapy. These viruses exploit the fact that cancer cells often have defective antiviral defenses, making them more susceptible to viral infection. Once inside the tumor cells, the virus replicates, causing the cells to burst and release tumor antigens. This process not only directly kills cancer cells but also primes the immune system to recognize and attack remaining tumor cells, offering a dual mechanism of action. Currently, two HSV-1-based oncolytic viruses, Imlygic (T-VEC) and DELYTACT, have been approved for the treatment of melanoma (U.S. and Europe) and recurrent glioblastoma (Japan), respectively. OncoD represents a significant step forward, offering a genetically stable platform for enhanced tumor targeting and immune modulation.

“HSV-1 is an excellent backbone for oncolytic virotherapy because it naturally infects a wide range of cells. By strategically modifying it, we’ve created a virus that is safer and more effective in killing tumors,” – explained Dr. Karina Vázquez-Arreguín, lead author of the study.

Engineering the OncoD Strain

Dr. Kaur and her team isolated a novel HSV-1 strain, UT1a, from a de-identified consented patient biorepository. Using CRISPR-Cas9 technology, the researchers deleted three key viral genes: UL39, UL40, and both copies of RL1. These deletions render the virus less harmful to normal cells while maintaining its ability to replicate in and kill tumor cells. Specifically, the deletion of UL39 and UL40 disrupts the virus’s ribonucleotide reductase activity, which is crucial for nucleotide metabolism in quiescent cells but upregulated in cancer cells due to their altered metabolism, thus enhancing tumor selectivity. The removal of RL1, which encodes the neurovirulence factor ICP34.5, further enhances the safety profile of the virus by preventing it affecting normal brain cells and enhances its safety profile.

Efficacy in Solid Tumor Models

In preclinical studies, OncoD demonstrated robust tumor-specific cytotoxicity and replication in various cancer cell lines, including glioblastoma, colorectal cancer, and lung cancer. Importantly, the virus showed no toxicity in normal cells and remained sensitive to the antiviral drug acyclovir, providing a safety net in case of adverse effects.
In mouse models, OncoD significantly improved survival in multiple tumor types, including glioblastoma and melanoma, and showed synergistic effects when combined with radiation therapy. Transcriptomic analysis revealed that OncoD impairs DNA damage repair pathways in cancer cells, making them more susceptible to radiation-induced cell death.
Dr. Kaur and her team believe that OncoD’s unique combination of safety, efficacy, and compatibility with existing therapies makes it a promising candidate for further development.

“OncoD not only kills tumor cells directly but also activates the immune system to fight cancer,” said Dr. Kaur. “Its ability to synergize with radiation therapy could significantly improve outcomes for patients with solid tumors.”

Oncolytic Viruses as Immunotherapy Agents

Beyond direct tumor destruction, oncolytic viruses like OncoD also function as immunotherapy agents by stimulating anti-tumor immune responses. When OncoD lyses tumor cells, it releases tumor-associated antigens, helping prime the immune system to recognize and attack residual cancer cells. This immune-stimulatory effect positions OncoD as a promising candidate for combination therapies that integrate checkpoint inhibitors, radiation therapy, or chemotherapy.

Future Clinical Applications

Given its favorable safety and efficacy profile, OncoD is a strong candidate for further clinical development. The team envisions using it not only as a standalone therapy but also in combination with existing cancer treatments such as radiation and immunotherapy.

“The ability to engineer viruses with precision is transforming how we approach cancer therapy. Our goal is to take OncoD into clinical trials and explore its potential in different types of cancers,” Dr. Kaur emphasized.

With the growing interest in oncolytic virotherapy, OncoD represents a significant step toward harnessing viral engineering for precision oncology. Further studies will focus on optimizing dosing, expanding tumor indications, and integrating it with other therapeutic modalities.

Reference

Vázquez-Arreguín, K. et al. Engineering a novel HSV-1 strain for oncolytic therapy of solid tumors. Molecular Therapy Oncology, 2025, 200961, DOI: 10.1016/j.omton.2025.200961

Disclaimer: This information is intended solely for research purposes and does not serve as medical advice.

 

About Marin Biologic Laboratories

Our Recent Publication/Meeting Presentation on Gene Therapy

American Society of Hematology (ASH) Annual Meeting 2024.

Abstract link: Using Gene Therapy to Solve Challenges with CAR-T Cell Immunotherapy: Lead Selection and Preclinical Development of an Adeno-Associated Virus with Reduced Immunogenicity Exhibiting Efficient and Long-Term Expression of an Anti-CD19 T-Cell Engager.

Comprehensive Assay Solutions for In Vitro and Cell Based Potency Assays and Pharmacokinetics Studies- Our Expertise

With 30 years of expertise in cell culture, cell-based assays, and preclinical/clinical PK/PD analysis, we specialize in offering assay services essential for a wide variety of therapeutic drug development programs, preclinical studies, IND/BLA applications, and commercialization. Our comprehensive services include both preclinical non-GLP and GLP assays, as well as non-GMP and GMP assays, providing critical support throughout the entire development pipeline.

Watch the following video and explore our latest presentation on the development and validation of potency and pharmacokinetic (PK) assays for AAV vectors, highlighting innovative methodologies and industry-leading expertise.

 

 

Download the full presentation: Development of Custom Cell Based and In vitro Potency and Pharmacokinetics (PK) Assays for AAV vectors- Marin biologic Laboratories

 

Development of Cell-Based Potency Assays: Case Studies and Blogs from Marin Biologic Laboratories (MarinBio)

 

Drug Discovery & Development Assays Offered by Marin Biologic Laboratories (MarinBio)