Expert Highlights Preclinical Activity Seen With Cowpea Mosaic Virus in Ovarian Cancer

Christa Dominick, MD

Christa Dominick, MD

For several decades, the cowpea mosaic virus, a virus infecting cowpeas primarily in West Africa, has been studied in various diseases. Data from the Steinmetz Lab at Case Western Reserve University suggest that this virus could delay growth of cancers and potentially improve survival rates for patients.

The research team at Steinmetz Lab began studying the possibility of combining this virus with standard treatments, such as doxorubicin (Adriamycin) or cisplatin (Platinol), for the treatment of patients with ovarian cancer. Results were recently shared from another study at University Hospitals in which investigators used a patient-derived xenograft (PDX) database of patient samples from The DiFeo Lab to examine the cowpea mosaic virus in patients with ovarian cancer.

In this preclinical trial looking at tumors in mice, the cowpea mosaic virus demonstrated a statistically significant difference in tumor growth in mice that received this treatment versus mice that received a placebo. Tumor weight decreased and was confined to smaller portions of the body.

In an interview withTargeted Oncology, Christa Dominick, MD, a gynecologic oncology fellow at University Hospitals, discussed the rationale behind this trial and the results. She also highlighted her plans moving forward with other trials involving the cowpea mosaic virus in ovarian cancer.

TARGETED ONCOLOGY: What is the cowpea mosaic virus and what was the rationale for using it for ovarian cancer?

Dominick:The cowpea mosaic virus is a virus that happens to infect plants. It specifically infects the cowpea. Normally, when the cowpea is not infected, it’s green. When it is infected, it turns a yellowish shade and looks like it has a mosaic pattern, which is why it's named that. It's a common virus and a common plant in West Africa. It has been studied extensively since the 1950s for various different things. Recently, Dr. Nicole Steinmetz's lab at Case Western Reserve University found that by injecting it into mice with different types of cancers, it has delayed the growth of cancers and improved survival rates.

When starting in The DiFeo Lab at Case Western Reserve University, we were thinking what we can do to meet University Hospital’s mission to teach, to heal, and to discover. We thought, well how do we apply this to our patients?

We are looking into an ovarian cancer model. The DiFeo Lab has a PDX database repository of patients who have consented and desire to be a part of a research team. We have those samples from patients that we have been able to put in mice, and we thought if this is working in mouse tumors and other tumors similar to patient tumors, I wonder if it would work for patients and their tumor. That's where the idea came from.

TARGETED ONCOLOGY: How did you design this study?

Dominick:The study was designed as a preclinical mouse study, so we took 20 mice and injected them with the PDX cell line. We waited for those tumors to grow large enough so that we can see them on a CAT scan. We then randomized and treated 10 of the mice with a placebo and 10 with the cowpea mosaic virus.

TARGETED ONCOLOGY: What were the findings from this study?

Dominick:It was actually very exciting. The cowpea mosaic virus actually did an excellent job. It had a statistically significant difference in tumor growth and distribution of the tumor. In the mice without any treatment at all, we saw tumor extensively throughout their abdomen and they had an average of 4-6 gram tumor weight, whereas the mice that had the cowpea mosaic treatment had an average of 2-4 gram tumor weight, which was a huge difference. You could actually see in the mice that their smaller abdomens just looked healthier. Their tumors were confined to the pelvis primarily, whereas the ones who didn't have this treatment had the tumor up by the liver, up by the spleen, and so there was a drastic difference when you were looking inside the mice.

TARGETED ONCOLOGY: What is the overall takeaway from these results?

Dominick:The overall takeaway from this study was that the cowpea mosaic virus actually does work to delay tumor growth in PDX models of high-grade serous ovarian cancer. We are really excited to keep testing it further.

TARGETED ONCOLOGY: In what ways do you plan to continue this testing in the future?

Dominick:We have a bunch of ideas, but we would like to try a similar study in a humanized mouse model. That means that what we have currently is a mouse with the mouse's immune system and there are various types of mice with various types of immune systems. What we can do is see how this virus is interacting with the human immune system, which is more clinically relevant to how it would be with our patients. To do that, there are a few institutions that implant, in various methods, human immune systems in the mice. A common one, for example, is the BLT method, which is essentially putting bone marrow, liver tissue, and thymus tissue into the mouse. Once it's been about 8 weeks after that, you can test your tumor on it. You're essentially testing a human immune system.

TARGETED ONCOLOGY: Are there any other studies in ovarian cancer you are particularly interested in?

Dominick:There are quite a few studies I am excited about. In The DiFeo Lab, they are working on finding a biomarker so that we can do a better job with screening. Right now, we don't have a good way to screen for ovarian cancer, so it's a big hold up. If we could find a way to screen for people and catch ovarian cancer at earlier stages, then we would be increasing survival dramatically and really helping our patients.

Similarly, in the Steinmetz Lab, there is the idea of combining the cowpea mosaic virus with other therapies we already have, such as doxorubicin or cisplatin, that are being used in ovarian cancer. We are wondering that if we combine this cowpea mosaic virus to those treatments, can we either decrease the need for systemic toxic chemotherapy or perhaps be able to give it less frequently or at a lesser dose. I'm excited for those results.