Oncolytic Virus Therapy: Novel Immunotherapeutic Approach to Treating Cancer
Oncolytic Virus Therapy: Novel Immunotherapeutic Approach to Treating Cancer
Blog Article
Oncolytic virus therapy, also known as oncolytic virotherapy, uses specially engineered viruses to selectively target and kill cancer cells. These viruses are genetically modified to replicate specifically in and destroy cancer cells while sparing normal cells. When the viruses infect and replicate within tumor cells, they cause the cells to lyse or rupture and die, releasing new virus particles to find and infect neighboring cancer cells in a repeating cycle of treatment. Over multiple cycles of selective viral infection and replication within the tumor, oncolytic viruses can potentially eliminate all cancer cells in the tumor.
History and Development of Oncolytic Viruses
Oncolytic Virus Therapy concept of using viruses to treat cancer is not new. As early as the 1950s, several viruses including Newcastle disease virus, mumps virus and influenza virus were observed to produce tumor regressions in some cancer patients. However, these results were inconsistent and significant toxicity limited further development. With advances in molecular biology and genetic engineering in the late 20th century, researchers gained the ability to genetically modify viruses and regulate their replication. This allowed the creation of safer, more cancer-specific oncolytic viruses. Some of the earliest genetically engineered oncolytic viruses included a herpes simplex virus modified to only replicate in rapidly dividing cells and a reovirus lacking an anti-apoptotic gene. In recent decades, additional genetically engineered oncolytic viruses targeting various cancer types have been developed using a variety of viral platforms.
Mechanisms of Action
Oncolytic viruses utilize multiple complementary mechanisms to fight cancer:
Direct cytolysis - When viruses infect and replicate within tumor cells, they trigger cell lysis or rupture, directly killing the infected cancer cells. Subsequent cycles of viral infection and replication kill neighboring tumor cells in a repeating cascade.
Viral antitumor immunity - Viral infection of tumor cells stimulates the patient's innate and adaptive immune responses against both the virus and the tumor. Oncolytic viruses act as in-situ vaccines by releasing tumor antigens during cell lysis, stimulating antigen-presenting cells and boosting T cell responses against the cancer.
Anti-angiogenic effects - Some viruses disrupt tumor vascular endothelial growth factor (VEGF) signaling, inhibiting new blood vessel formation critical for tumor growth and metastasis.
Bystander killing - Infected tumor cells release virus particles that kill nearby uninfected tumor cells through cellular signaling apoptosis pathways.
Integration with other therapies - Oncolytic viruses can enhance responses to other immunotherapies like checkpoint inhibitors by promoting inflammation and an active anti-tumor immune response in the tumor microenvironment.
Specificity and Safety of Oncolytic Virus Therapy
To achieve selective replication within cancer cells, oncolytic viruses are genetically modified with deletions or mutations in nonessential genes required for replication in normal cells. Common targeting strategies include promoting viral replication dependence on dysregulated cellular signaling pathways frequently activated in cancer cells like ras/raf/MEK or components of the tumor microenvironment like hypoxia-inducible factor 1-alpha. Additional mechanisms restricting toxicity include transcriptional targeting that selectively drives viral gene expression in tumor versus normal cells.
Safety is rigorously tested in preclinical models and clinical trials. To date, oncolytic virus therapies have proven well-tolerated, with mostly flu-like symptoms reported as adverse events. While immunocompromised patients were initially excluded from clinical trials over theoretical concerns, emerging data now suggest even these patients can be safely treated with appropriate safety protocols. Dose, virus strain and administration route are also tailored and monitored closely to maximize safety and efficacy for each virus candidate.
Approved Oncolytic Virus Therapy and Ongoing Clinical Development
To date, two oncolytic viruses have received regulatory approval. Talimogene laherparepvec (T-VEC) was the first oncolytic virus approved by the FDA in 2015 for the treatment of melanoma. T-VEC is a genetically modified herpes simplex virus type 1 engineered to produce GM-CSF, stimulating antitumor immunity. In a phase III trial, T-VEC improved durable response rates compared to subcutaneous GM-CSF alone in advanced melanoma.
In China in 2005, H101, an adenovirus modified to replicate only in cancer cells deficient in p53 tumor suppressor gene function, was approved for head and neck cancer treatment. Additional oncolytic virus candidates in late-stage testing across a range of cancer types include pelareorep, a reovirus for breast and other solid tumors, and Newcastle disease virus candidate NDV-Hu, targeted against soft tissue sarcoma and glioma brain cancer. Multiple other novel viral platforms including vaccinia virus, coxsackievirus and seneca valley virus are also undergoing active clinical evaluation worldwide.
Future Perspectives and Combination Therapies
Ongoing research aims to enhance the potency and breadth of oncolytic viruses. Strategies involve further engineering viruses to overcome tumor resistance mechanisms, increase viral spread and production, and stimulate antitumor immunity. Combination therapies are also emerging as an important avenue, with oncolytic viruses being paired with immunotherapy checkpoint inhibitors, targeted therapies, radiation therapy, and in some cases other oncolytic viruses. Carefully designed combination regimens hold promise to improve outcomes over single agent therapy by leveraging complementary and synergistic mechanisms of action. If safety and efficacy continue to be demonstrated, oncolytic virus therapy may become an important new treatment option either alone or in combination for a wide range of cancers in the coming years.
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Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemical and materials, defense and aerospace, consumer goods, etc. (https://www.linkedin.com/in/money-singh-590844163