Cancer is one of the leading causes of deaths worldwide. Despite ongoing research and new drugs, conventional treatment options like chemotherapy, radiation therapy and surgery are not always effective and come with severe side effects. Oncolytic virus therapy is an emerging and promising treatment approach that uses genetically engineered viruses to selectively target and kill cancer cells.

What are Oncolytic Viruses?

Oncolytic viruses, also called replication-selective viruses or oncolytic vectors, are genetically modified viruses that preferentially infect and kill cancer cells while sparing normal cells. Researchers alter the virus' genome so that it loses its ability to replicate in normal cells but retains or enhances its ability to infect and destroy cancer cells. Several types of DNA and RNA viruses, both naturally occurring and engineered, are being studied for their oncolytic potential against various cancers.

Mechanism of Action

Oncolytic viruses work via multiple mechanisms that exploit the differences between normal and cancer cells. Firstly, cancer cells often have defective antiviral response pathways that viruses can exploit to preferentially infect them. Secondly, some viruses induce cancer cell lysis or death by viral replication within the cell. As the virus replicates, it causes the cancer cell to burst and die, releasing new virus particles to infect neighboring tumor cells. Thirdly, the viral infection stimulates anti-tumor immune response by the host which helps eliminate residual and metastatic cancer cells.

Advantages over Conventional Therapy

Oncolytic virus therapy offers several potential advantages:

- Selectivity: Viruses are designed to replicate specifically in cancer cells, sparing normal cells, reducing side effects.

- Amplification: Viral replication within tumors leads to amplification and spreading of the therapy throughout the tumor mass.

- Immune stimulation: Viral infection activates anti-tumor immunity providing durable response.

- Combination therapy: Can be combined with chemotherapy, radiation, immunotherapy to enhance efficacy.

- Novel mechanism: Provides an alternative treatment option for cancers resistant to standard therapies.

Ongoing Clinical Trials

Several Oncolytic Virus Therapy have entered clinical trials over past decades, with some gaining regulatory approval. Some notable examples are:

- Talimogene laherparepvec (T-VEC): First FDA approved oncolytic virus for melanoma. Phase 3 trial showed improved durable response rate compared to GM-CSF alone.

- Oncorine (H101): Conditionally replicating adenovirus approved in China for nasopharyngeal carcinoma based on Phase 3 trials showing improved survival.

- Pelareorep (Reolysin): Phase 2 trials show promise in breast, head & neck cancers when given with chemotherapy. Ongoing Phase 3 trial in metastatic breast cancer.

- CG0070 (Cavatak): Oncolytic Coxsackie virus in clinical trials for glioblastoma, melanoma and pancreatic cancers.

- Numerous other viruses are under investigation including vaccinia virus, Newcastle disease virus and others against various solid tumors.

Challenges and Future Directions

While oncolytic virus therapy is promising, some challenges remain. Difficulty in achieving sufficient viral doses at the tumor sites, neutralization by host’s antiviral immunity and safety issues needs to be addressed. Future areas of research include:

- Developing improved viral delivery methods like conjugation to tumor-targeting ligands.

- Combination with checkpoint inhibitors and other immunotherapy to enhance response.

- Engineering multi-mechanistic viruses armed with immune modulatory transgenes.

- Wide-ranging clinical evaluation across more tumor types.

Oncolytic virus therapy is an innovative approach that harnesses the natural ability of viruses to target cancer cells. With ongoing research optimizing viral vectors and combining with other modalities, it holds great potential to revolutionize cancer treatment in the years to come.

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