Lung cancer remains a major global health challenge, causing many cancer-related deaths each year. Despite advancements in conventional therapies, innovative approaches are still needed. Oncolytic virotherapy, which uses viruses to fight cancer, is a promising new strategy.
Harnessing Viruses for Cancer Therapy
Oncolytic viruses (OVs) are naturally occurring or genetically modified viruses designed to selectively infect and destroy cancer cells while leaving healthy tissues unharmed. The concept of using viruses to treat cancer, or “virotherapy,” dates back to the late 19th and early 20th centuries. Early observations of cancer regression in patients with natural viral infections sparked initial interest. Early trials involved administering virus-containing fluids, but success was limited because the immune system often neutralized the viruses.
Genetic engineering in the 1990s shifted the view of viruses from pathogens to potential therapeutic agents. This allowed scientists to modify viruses, enhancing their ability to target and replicate within cancer cells while minimizing harm to normal cells. This selective targeting makes oncolytic viruses a promising avenue in fighting various cancers, including lung cancer. OVs can amplify within the tumor itself, a characteristic not seen in typical pharmacological agents.
Mechanisms of Viral Action in Lung Cancer
Oncolytic viruses fight lung cancer through two main mechanisms: direct cancer cell lysis and immune system activation. These viruses are engineered or naturally infect tumor cells. Once inside, they replicate within these malignant cells, leading to their destruction.
This process, known as oncolysis, causes infected cancer cells to burst and die, releasing new viral particles to infect neighboring tumor cells. The destruction of cancer cells also releases tumor-specific antigens and danger signals into the tumor microenvironment. These components alert the body’s immune system.
The immune system then recognizes these antigens as foreign, initiating a broader anti-tumor immune response. This activation can involve the recruitment and activation of immune cells, such as T cells, natural killer (NK) cells, and macrophages. This immune response can target and eliminate not only directly infected tumor cells but also distant metastases.
Clinical Progress in Viral Lung Cancer Therapies
Oncolytic virotherapy for lung cancer has made progress, with many viruses under investigation in clinical trials. Viruses being explored include modified adenoviruses, herpesviruses, measles virus, and vaccinia virus. These investigations are primarily concentrated in the United States, China, and Europe.
Many therapies are in early-phase clinical trials (Phase I or II), but no successful Phase III trials for lung cancer have been reported yet. A milestone for the field was the FDA approval of talimogene laherparepvec (T-VEC) in 2015 for advanced melanoma. T-VEC, a modified herpes simplex virus type 1, was the first oncolytic virus approved in the Western world, setting a precedent for this therapy class.
For lung cancer, research includes combination therapies where oncolytic viruses are used alongside other treatments like immunotherapy or chemotherapy. For example, a clinical trial is underway for patients with late-stage non-small cell lung cancer, combining an oncolytic adenovirus (MEM-288) with the immune checkpoint inhibitor nivolumab. This combination aims to destroy tumor cells, enhance the immune response, and overcome immune suppression within the tumor microenvironment.
Patient Considerations and Outlook
Patients considering oncolytic virotherapy for lung cancer should be aware of potential side effects, which are generally mild and transient. Common reactions often resemble flu-like symptoms, including fatigue, fever, chills, headaches, muscle aches, nausea, vomiting, and diarrhea. These symptoms are typically most pronounced within the first few administrations and tend to lessen over time.
Oncolytic viruses are often administered by direct injection into the tumor, known as intratumoral delivery. This approach allows for targeted treatment, minimizing exposure to healthy tissues and reducing premature immune neutralization. Less common but more severe side effects can occur, such as cellulitis, shortness of breath, increased heart rate, fluid buildup in the chest, or low blood pressure.
The safety profile of oncolytic virotherapy is favorable, and research continues to refine these treatments for improved patient outcomes. The future potential of oncolytic virotherapy for lung cancer is considerable, with research focused on optimizing virus design, enhancing specificity, and improving clinical efficacy. Integrating these viral therapies with other treatment modalities offers a promising new avenue in lung cancer treatment.