Herpes: The Potential Breakthrough in Cancer Therapy

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8كيلو بايت

Scientists are developing all sorts of potential new treatments to tackle the most difficult cancer cases—including some that will make you thankful for the existence of herpes and other viruses. Clinical trial data out today shows that a modified version of the herpes simplex virus 1 (HSV-1) can help keep late-stage skin cancer at bay.

Researchers at the University of Southern California and others conducted the study, a Phase I/II trial of people with advanced, treatment-resistant melanoma. About a third of patients given the modified virus, in combination with immunotherapy, saw their tumors substantially shrink, while some even experienced a complete regression of their cancer. A larger, definitive trial of the experimental therapy, code-named RP1, is already underway, and the Food and Drug Administration will decide on an approval later this month.

Scientists have been intrigued about the promise of cancer-fighting, or oncolytic, viruses for over a century, according to study author Gino In, a medical oncologist at USC’s Keck School of Medicine. But it’s only recently that this potential has started to look within reach.

“Most progress has been made just in the last few decades, thanks to advances and progression in gene editing technologies, which have allowed researchers to specifically design oncolytic viruses that are more effective and safer,” In told Gizmodo.

HSV-1, the primary cause of cold sores, has emerged as a particularly promising candidate for cancer treatment. HSV-1 is a relatively large virus, meaning scientists can replace or add new genes without too much trouble. And though it does use our cells to replicate, like any virus, it doesn’t insert its DNA into a cell’s genome directly, eliminating the risk of certain mutations (an important consideration for safety). A typical HSV-1 infection also isn’t life-threatening and can be treated with antiviral medications if needed, further limiting its potential danger.

These properties have allowed scientists to create strains of the virus that can selectively target cancer cells. The first herpes-based cancer therapy (T-VEC) was approved in the U.S. in 2015 for some cases of metastatic melanoma. But researchers like In are especially excited by the new generation of these treatments.

RP1 is the brainchild of biotech company Replimune, and it’s one of several cancer-fighting viruses that the company is currently developing. Compared to the typical HSV-1 virus, RP1 has been weakened, meaning it shouldn’t be able to cause severe infections. It’s also been modified to not only target cancer cells, but to also boost the immune system’s natural tumor-killing ability.

“These changes make RP1 both safer and better at killing cancer cells than natural HSV-1,” In explained. And while RP1 might be a viable treatment on its own, Replimune is also testing whether it can be even more effective when paired with other existing immunotherapies.

This latest study involved 140 patients from the company’s IGNYTE trial of RP1 conducted across several sites, including at USC. The participants had late-stage melanoma that was unresponsive to earlier immunotherapy treatment. They received both RP1 and nivolumab, an immunotherapy drug commonly used for melanoma, every two weeks for up to four months. If patients responded to the initial treatment, they continued taking nivolumab alone for up to two years.

By the study’s end, a third of patients saw their tumors decrease in size by at least 30%, the researchers found, and almost one in every six patients had their tumors disappear entirely. Importantly, this shrinkage was seen in tumors directly injected with RP1 as well as uninjected tumors throughout the body—indicating its immune-boosting potential worked as hoped. The combination therapy also appeared to be safe, with most patients only experiencing minor adverse events like fatigue or other flu-like symptoms.

The findings were presented earlier this year at the annual meeting of the American Society of Clinical Oncology and were published Tuesday in the Journal of Clinical Oncology.

“This study provides an important new approach for patients with immunotherapy-refractory melanoma; this is very important since about half of all melanoma patients do not benefit from immunotherapy,” said In. “So it provides a new type of treatment, one that is both effective and well tolerated.”

Early trials are primarily intended to vet an experimental treatment’s safety and optimal dosing, not its effectiveness. But given the general outlook of these normally untreatable cases, there’s certainly reason to be optimistic here.

Last year, Replimune launched a Phase III trial that will test RP1 combined with nivolumab in around 400 people with treatment-resistant melanoma. But even before this study concludes, RP1 could become available to the public. In January, the FDA agreed to consider the combination therapy for accelerated approval, a process that allows a novel treatment to be tentatively approved with less direct evidence of its effectiveness (further trial data is still required to secure a full approval). The FDA’s decision on RP1 is scheduled for July 22.

In and the USC team will continue to study their data to better understand how RP1 works. But they expect RP1 to become a new option for these resistant melanoma cases, and In notes that RP1 is also being tested for other kinds of cancer. If things keep going right, virus-based therapies like RP1 could soon become the next frontier of cancer treatment.

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