At the 2023 Society of Gynecological Oncology’s Annual Meeting on Women’s Cancer in Tampa, Florida, Ayesha Alvero, MD, C.S. Mott Center at Wayne State University, Detroit, Michigan, discusses the use of the novel immunomodulatory virus CARG-2020 to restore immunosurveillance and establish anti-tumoral immunological memory to prevent ovarian cancer recurrence.

Dr Alvero covered next steps for this research, how CARG-2020 might eventually fit into the treatment paradigm, and potential toxicities, and future implications of this treatment for patients with ovarian cancer.

Transcript

I am Ayesha Alvero. I am a professor in the Department of Obstetrics and Gynecology at C.S. Mott Center, which is in Wayne State University in Detroit. We are currently at the Society of Gynecological Oncology Annual Meeting 2023 in Tampa, Florida.

I presented work on CARG-2020, which is a novel immunomodulatory virus. The objective of our study is to leverage host immune response to prevent recurrent ovarian cancer, which is a big ask, I know.

What we hypothesize is that to be able to do that we should be able to develop a strong immune memory. The hypothesis is that to get there, we would need to modulate both the innate and the adaptive arms of the immune system. We constructed an immune modulatory virus that's able to improve antigen presentation, promote the expansion of cytotoxic T-cells that would eventually kill tumors, inhibit what's called the immune checkpoint, that is preventing the host immune system from attacking and continuously attacking the cancer cells, as well as an oncolytic virus component that's able to induce cell death and improve the antigenicity of the tumor.

And what we saw is that CARG-2020 can induce complete disease regression in mice bearing ovarian cancer, improving overall survival. What's even more interesting is then when these animals are rechallenged, later we see complete prevention of tumor formation, suggesting that we have created immune memory.

What are the next steps for this research?

Right now, we are developing the modality to be manufactured in clinical grade manufacturing practices and setting up to begin the FDA application for phase 1 clinical trials.

How does this fit into the existing treatment paradigm?

You cannot ask the immune system to tackle big tumors. We expect this to be given after standard of care. In the clinic we are very good in treating primary disease, but then once it recurs that's where the problem lies. We think that the placement of this would be as maintenance therapy or at least after standard of care.

Do you have an idea of what the toxicities might be?

What we set out to do in the mice is to identify our maximum-tolerated dose. Then as you scale back, you realize that you are seeing efficacy without seeing this toxicity. This therapeutic window does exist. It's related to a viral infection, where in your body detects that there is something there and tries to protect you. We see mice kind of having chills when we give them a dose that's a little bit higher than what they can take.

What are the future implications for patients?

Most patients with ovarian cancer would succumb from recurrent disease. Usually when they get to recurrent ovarian cancer, very chemotherapy-resistant, there is nothing really that is available. Being able to say that we have this modality that's able to prevent that, then that would be a big game changer.

Source:

Alvero, A. “Immune modulation of innate and adaptive responses by CARG-2020 restore immunosurveillance and establish anti-tumoral immunological memory.” Presented at SGO Annual Meeting on Women's Cancer; March 25-28, 2023; Tampa, FL