Herpes Viruses Against Cancer: FDA Approves a Second HSV-Based Melanoma Drug

Herpes simplex virus is best known for cold sores and genital herpes, but modified versions of it are now approved cancer drugs. On August 6, 2026, the FDA granted accelerated approval to Replimune's RP1 (vusolimogene oderparepvec, brand name Tudriqev) in combination with nivolumab (Opdivo) for advanced melanoma that has progressed after immunotherapy.

It is the second herpes-based cancer therapy approved in the US, after Amgen's talimogene laherparepvec (T-VEC, Imlygic) in 2015.

A separate line of research uses proteins borrowed from a different herpesvirus to keep immune cells working inside tumors. Both approaches turn tools the virus evolved to manipulate cells into cancer treatments.

None of these therapies can give you herpes. The viruses are engineered so they can only replicate in cancer cells.

Oncolytic herpes viruses infect and destroy tumor cells

Oncolytic means "cancer-breaking." These therapies use HSV-1 with genes removed so it can't cause disease in healthy tissue. Cancer cells often have weakened antiviral defenses, so the modified virus can replicate inside them and burst them open.

When the tumor cells break apart, they release tumor proteins that the immune system can learn to recognize. The viruses are also engineered to carry extra genes, such as GM-CSF, that call in immune cells. The result is an immune attack that can reach tumors the virus never touched.

The virus is injected directly into tumors in the skin, lymph nodes or, in newer trials, internal organs. Common side effects are flu-like symptoms such as fever, chills and fatigue, plus reactions at the injection site.

RP1 won approval after two rejections

RP1 is an HSV-1 virus armed with GM-CSF and a protein (GALV-GP) that makes tumor cells fuse together and die. Replimune tested it with nivolumab in the IGNYTE trial in people whose melanoma kept growing despite PD-1 immunotherapy, a group with few options.

The FDA turned down the application twice, mainly over questions about whether a single-arm trial could show how much benefit came from RP1 rather than nivolumab. In July 2026 an FDA advisory committee voted 10 to 3 that the data showed the combination works. The agency approved it on August 6, 2026.

The approval is "accelerated," meaning it depends on a confirmatory Phase 3 trial, IGNYTE-3, expected to report in late 2027.

RP2 is in a key trial for eye melanoma

RP2 is a related HSV-1 virus that also carries an antibody blocking CTLA-4, an immune brake. It is being developed for metastatic uveal melanoma, a rare melanoma of the eye that often spreads to the liver and responds poorly to standard immunotherapy.

Final Phase 1 data presented at ASCO 2026 showed responses in about a third of uveal melanoma patients treated with RP2-based therapy, and many responses lasted more than a year.

The REVEAL trial is comparing RP2 plus nivolumab with ipilimumab plus nivolumab in about 280 patients. It is enrolling now, with the move from Phase 2 to Phase 3 expected in early 2027.

Other HSV-based cancer therapies in development include MB-108, which has FDA orphan drug designation for malignant glioma and is being tested alongside CAR-T cell therapy for recurrent glioblastoma.

A borrowed herpesvirus protein keeps T cells active

A May 2025 study in Science Immunology took a different approach. It used herpesvirus saimiri, a virus that infects T cells in squirrel monkeys without causing disease. One of its proteins, called TIP, switches on a signaling pathway inside T cells called JAK-STAT5, which keeps them alive and active.

Normally, T cells need the signaling molecule interleukin-2 (IL-2) to activate STAT5. Tumors suppress IL-2, which is one reason T cells stop working inside them, and giving IL-2 as a drug causes serious side effects.

The researchers engineered a version of TIP that recruits a kinase called LCK to activate STAT5 directly, with no IL-2 needed. T cells carrying the engineered protein kept working inside tumors and killed cancer cells more effectively in mouse models of melanoma and lymphoma.

The protein approach could boost CAR-T therapy

CAR-T therapy, where a patient's T cells are engineered to attack their cancer, works well in some blood cancers but often fails in solid tumors because the tumor environment shuts the T cells down. Adding an engineered viral protein that keeps STAT5 switched on could help CAR-T cells survive in that environment.

Other teams are combining oncolytic HSVs with CAR-T cells. In pancreatic cancer models, the virus made tumors more visible to the immune system, increasing killer T cells and dendritic cells and reducing regulatory T cells that suppress the attack.

The TIP work is still preclinical. It has not been tested in people.

What this means if you have herpes

These therapies use heavily modified viruses and have no bearing on how you manage your own HSV-1 or HSV-2. Having herpes does not protect you from cancer, and you cannot catch herpes from a patient receiving an oncolytic virus through casual contact, although patients are advised to cover injection sites.

Some patients receiving these treatments do have herpes already. Trials have generally allowed this, and existing antibodies have not stopped the therapy from working when injected directly into tumors.

For herpes treatment news, see our herpes cure research update.

Sources:

• An engineered viral protein activates STAT5 to prevent T cell suppression, PubMed
• An engineered viral protein activates STAT5 to prevent T cell suppression, Science Immunology
• FDA approves Replimune melanoma drug previously rejected twice, STAT