Written By: Devin Golden
ONCOS-102: Promising Oncolytic Virus for Mesothelioma
ONCOS-102 is an emerging treatment for mesothelioma, which is a rare and aggressive cancer caused by asbestos exposure. This therapy uses genetically altered viruses to cause mesothelioma tumor cells to break up and create a tumor-specific immune response in the body. This response from the immune system enhances the body’s ability to fight the cancer.
Medically Reviewed By
Dr. Stephen Williams
Precision Oncology Scientist
Medically Reviewed By
Dr. Stephen Williams
Precision Oncology Scientist
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Important Facts About ONCOS-102 for Mesothelioma
- ONCOS-102 is an oncolytic adenovirus that breaks up cancer cells and sends signals to the immune system to fight cancer.
- The therapy sends a virus into mesothelioma cells. The cells then burst, causing a release of antigens, the fingerprints of the tumor, allowing the T cells to recognize mesothelioma cells.
- ONCOS-102 received FDA fast-track designation early in 2021. This grants speedier approval and review procedures for the therapy.
- A study using ONCOS-102 plus chemotherapy outperformed chemotherapy alone by a median survival of seven months. The one-year survival rate also was better due to ONCOS-102.
- The manufacturer, Targovax, plans to use ONCOS-102 with an immunotherapy drug in future trials, hoping to further stimulate an immune response to target mesothelioma.
What Is ONCOS-102?
ONCOS-102 is an oncolytic virus for mesothelioma engineered to selectively infect and destroy cancer cells. The virus carries cytokines that stimulate a quick and powerful immune response.
How Does ONCOS-102 Work?
ONCOS-102 is an oncolytic virus that can infect mesothelioma cells and stimulate the immune system to target and eliminate other cancer cells. This mechanism makes it a promising treatment for mesothelioma.
Below is a step-by-step explanation of how ONCOS-102 works.
Step 1: Selective Infection and Tumor Cell Destruction
ONCOS-102 is injected directly into the tumor site. The virus is engineered to selectively infect mesothelioma cells, sparing healthy tissue.
Once inside the tumor, ONCOS-102 replicates, causing the infected cancer cells to rupture and die. This activity not only disrupts tumor growth but also exposes the tumor cell DNA to the immune system.
Step 2: Activation of the Immune System
Under normal circumstances, mesothelioma evades the immune system by creating an immunosuppressive tumor microenvironment. However, when ONCOS-102 causes tumor cells to break apart, they release antigens into the surrounding tissue.
Antigens are specific fingerprints that make up the cancer cells. When they are released, the fingerprints become the evidence the immune system needs to attack other diseased cells.
“What’s really interesting about viruses is they’re able to kill cancer cells so that the cancer cells become visible to the immune system,” explained Dr. Magnus Jaderberg, the Chief Medical Officer for Targovax, the manufacturer of ONCOS-102. “That’s the underlying principle of ONCOS-102.”
Step 3: Transition to Immunotherapy with GM-CSF
Beyond simply destroying cancer cells, ONCOS-102 is designed to enhance the immune response by delivering an immune-stimulating transgene. The virus carries a cytokine that recruits and activates key immune cells to the area where the cancer exists.
This cytokine prompts dendritic cells, which are antigen-presenting cells, to migrate to the tumor site and gather the released antigens. The dendritic cells then provide the antigen information, the tumor’s fingerprints, to the T cells, which are the immune system’s primary soldiers against diseases.
Step 4: Systemic Anti-Tumor Immune Response
Once the T cells have the tumor’s genetic information, they circulate through the body hunting down other cancer cells with the same genetics. This process transforms ONCOS-102 from a localized virotherapy into a systemic tumor-specific immune response.
This transformation potentially leads to long-term memory for the patient’s immune system of what the mesothelioma cancer looks like at the cellular level. This evolution of the immune system can prevent the cancer from returning (recurrence).
ONCOS-102 and FDA Approval for Mesothelioma
The U.S. Food and Drug Administration (FDA) granted a fast-track designation to ONCOS-102 for the treatment of malignant pleural mesothelioma. The fast-track designation is designed to expedite the development and regulatory review of promising therapies that address serious diseases with unmet medical needs. Mesothelioma falls into this category due to poor survival rates and limited treatment options.
Why ONCOS-102 Received Fast-Track Designation
The FDA’s decision to fast-track ONCOS-102 was based on promising clinical trial results demonstrating its potential efficacy in mesothelioma patients.
- Malignant pleural mesothelioma is an aggressive cancer with a poor prognosis, with a median survival of 12-18 months following diagnosis.
- When combined with chemotherapy, ONCOS-102 led to a median overall survival of 20.5 months compared to 13.5 months for chemotherapy alone.
- ONCOS-102 shows immunological benefits, such as increasing tumor-infiltrating T cells, a key indicator of prolonged immune response and better treatment outcomes.
- 90% of patients receiving ONCOS-102 plus chemotherapy experienced disease stabilization or tumor shrinkage.
- 64% of patients receiving ONCOS-102 plus chemotherapy survived for longer than one year.
Benefits of Fast-Track Designation for ONCOS-102
Fast-track designation provides several advantages that could accelerate an FDA approval of ONCOS-102:
- More frequent FDA meetings – Targovax, the biotech company that manufactures ONCOS-102, will have ongoing discussions with the FDA regarding clinical trial designs and necessary data collection for approval.
- Accelerated communication – Targovax will receive prompt, written guidance from the FDA to refine trial methodologies and regulatory requirements.
- Eligibility for accelerated approval and priority review – ONCOS-102 may qualify for priority review, allowing the FDA to assess sections of the New Drug Application on a rolling basis, expediting the final approval process.
ONCOS-102 Combined With Other Mesothelioma Treatment Options
Scientists are exploring combinations of ONCOS-102 and other treatment options for mesothelioma. The first studies tested ONCOS-102 with mesothelioma chemotherapy, which showed promise and led to the FDA granting a fast-track designation.
Next, scientists are considering ONCOS-102 combined with either immunotherapy or surgery.
ONCOS-102 and Immunotherapy for Mesothelioma
ONCOS-102 helps the immune system respond to the presence of mesothelioma cancer cells. In past and ongoing trials, ONCOS-102 is used as a multimodal therapy being paired with chemotherapy. It may also pair well with mesothelioma immunotherapy.
Dr. Magnus Jaderberg, Chief Medical Officer of Targovax, discussed these upcoming trials in a podcast interview with Mesothelioma Guide, expressing enthusiasm for this pioneering research. He highlighted the significance of collaborating with world-renowned institutions such as Memorial Sloan-Kettering Cancer Center and the Mayo Clinic to conduct portions of the study in the United States.
“This trial is the first time anyone has combined an oncolytic virus with a checkpoint inhibitor for this specific disease,” Dr. Jaderberg stated.
Targovax is planning a future clinical trial with ONCOS-102 and immune checkpoint inhibitors. Opdivo and Yervoy, two checkpoint inhibitor immunotherapy drugs, received FDA approval in 2020 for unresectable malignant pleural mesothelioma.
ONCOS-102 as a Maintenance Therapy After Surgery
ONCOS-102 might be beneficial following surgery to prevent postoperative recurrence.
Many patients undergo aggressive mesothelioma surgery, such as extrapleural pneumonectomy or pleurectomy/decortication, to remove mesothelioma tumors. However, the risk of recurrence remains high.
Researchers believe ONCOS-102 could be used after surgery to prevent recurrence by helping the immune system fight any remaining cancer cells.
The Future of ONCOS-102 in Mesothelioma Treatment
The exploration of ONCOS-102 as a multimodal therapy underscores the shift towards the use of immunotherapy as a treatment for mesothelioma. By combining ONCOS-102 with chemotherapy or checkpoint inhibitors, researchers aim to improve survival rates and quality of life for mesothelioma patients. If ongoing and future clinical trials prove successful, ONCOS-102 could become a key component in the evolving landscape of mesothelioma treatment strategies.
As research progresses, mesothelioma patients and their families should stay informed about clinical trials for emerging therapies. The potential of ONCOS-102, alongside advancements in immunotherapy, represents a promising step forward in the fight against this challenging disease.
Frequently Asked Questions About ONCOS-102 for Mesothelioma
What is ONCOS-102?
ONCOS-102 is an oncolytic virus, which is a genetically altered virus armed with a powerful immune-stimulating feature. The virus causes mesothelioma cells to break apart, which causes the release of tumor antigens and cytokines. These help the immune system track other mesothelioma cells with similar antigens and cytokines.
Is ONCOS-102 approved by the FDA?
No, ONCOS-102 is not yet approved by the FDA. However, it has received fast-track designation from the FDA for malignant pleural mesothelioma, which is the most common type of mesothelioma. A fast-track designation is an important step in the regulatory process. This designation is granted to therapies that address serious conditions and have the potential to fulfill an unmet medical need.
How long do people with mesothelioma live after receiving ONCOS-102?
ONCOS-102 survival rates exceed those of standard mesothelioma chemotherapy. The oncolytic virus thrived in clinical trials consisting mostly of people with late-stage mesothelioma cancer (stage 3 or stage 4). ONCOS-102 in combination with chemotherapy had a median survival of 20.5 months. The two-year survival rate is just below 50%.
Sources & Author
- Targovax ASA Webcast. Royalcast. Retrieved from: https://channel.royalcast.com/hegnarmedia/#!/hegnarmedia/20200121_1. Accessed: 01/28/2020.
- ONCOS-102. Immuno-Oncology News. Retrieved from: https://immuno-oncologynews.com/oncos-102/. Accessed: 01/28/2020.
- ONCOS -102 Mechanism of Action. YouTube. Retrieved from: https://www.youtube.com/watch?time_continue=32&v=K_PfmBpa38A&feature=emb_title. Accessed: 01/28/2020.
- ONCOS – Oncolytic Virus. Targovax. Retrieved from: https://www.targovax.com/en/oncos-oncolyctic-virus/. Accessed: 01/28/2020.
- Continued survival benefit in Targovax’s ONCOS-102 trial in mesothelioma at the 21-month follow-up. PRNewswire. Retrieved from: https://www.prnewswire.com/news-releases/continued-survival-benefit-in-targovaxs-oncos-102-trial-in-mesothelioma-at-the-21-month-follow-up-301233073.html. Accessed: 02/23/2021.
- Targovax demonstrates encouraging survival data for ONCOS-102 in mesothelioma. PRNewswire. Retrieved from: https://www.prnewswire.com/news-releases/targovax-demonstrates-encouraging-survival-data-for-oncos-102-in-mesothelioma-301179436.html/. Accessed: 12/29/2020.
- Fast Track. U.S. Food and Drug Administration. Retrieved from: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track. Accessed: 03/23/2021.
