Novel Stem Cell Therapy Harnesses Herpes Virus to Attack Melanoma

Stem cells carrying oncolytic herpes simplex virus effective against cancer that has metastasized to the brain.

Once cancer metastasizes to the brain, there are few effective treatments. Stem cells that harness the power of viruses may play a key role in stopping this process, according to a new study published by PNAS.

The study authors have developed cancer-killing viruses that can be delivered by stem cells, which has been observed to attack and kill metastatic melanoma cells in the brains of mouse models.

The authors believe that this stem cell-based therapy could also be combined with immune checkpoint inhibitors to elicit a stronger immune system response, according to the study.

“Metastatic brain tumors — often from lung, breast or skin cancers – are the most commonly observed tumors within the brain and account for about 40% of advanced melanoma metastases. Current therapeutic options for such patients are limited, particularly when there are many metastases,” said lead researcher Khalid Shah, MS, PhD. “Our results are the first to provide insight into ways of targeting multiple brain metastatic deposits with stem-cell-loaded oncolytic viruses that specifically kill dividing tumor cells.”

In a search for novel targeted therapies that could attack brain metastases without damaging healthy tissue, the authors first created different BRAF mice that closely model human disease.

The investigators found that injecting patient-derived, brain-seeking melanoma cells into the carotid artery of the mice resulted in many metastatic tumors throughout the brain, which is observed in advanced melanoma, according to the study.

The authors reported that the injected cells expressed markers that allow them to enter the brain and are bioluminescent and fluorescent for imaging purposes.

In an effort to create a novel treatment, the authors created stem cells derived from bone marrow that were loaded with oncolytic herpes simplex virus (oHSV). This virus is known to kill cancer cells, but does not affect healthy cells.

Previously, the researchers found that certain types of stem cells are attracted towards brain tumors. After determining that the stem cells injected to the brain would travel to multiple metastatic sites and not to healthy tissue, the team injected oHSV-loaded stem cells into the carotid artery of the mice, according to the study.

The authors found that injecting the stem cells into the carotid artery resulted in a significantly reduced tumor growth rate. This method was also found to increase survival compared with treatment with normal stem cells or placebo injections, according to the study.

The authors believe that this method of administration could be a promising strategy for clinical treatment.

Additionally, the oHSV-loaded stem cells are killed by oHSV-mediated oncolysis. Since this prevents the cells from living within the brain, oncolysis may be an important safety mechanism for this treatment, according to the study.

Through an immunocompetent melanoma mouse model, the authors investigated treating the animals with stem cells loaded with oHSV and immune checkpoint inhibitors. They discovered that PD-L1 checkpoint inhibitors improved the efficacy of stem cell-based oncolytic virotherapy in melanoma that has metastasized to the brain, according to the study.

“We are currently developing similar animal models of brain metastasis from other cancer types as well as new oncolytic viruses that have the ability to specifically kill a wide variety of resistant tumor cells,” Dr Shah concluded. “We are hopeful that our findings will overcome problems associated with current clinical procedures. This work will have direct implications for designing clinical trials using oncolytic viruses for metastatic tumors in the brain.”