Ryan Kahn, MD, MHS, gynecologic oncology surgery fellow, Memorial Sloan Kettering Cancer Center, discusses the investigation of Newcastle disease virus encoded with interleukin 12 (IL-12) in ovarian cancer.

Unlike the treatment of patients with cervical or uterine cancer, single-agent immunotherapy has not displayed efficacy in the treatment of patients with ovarian cancer. Finding ways to increase the effectiveness of immunotherapy in this group of patients could help address a key unmet need, Kahn says.

In prior studies, investigators at Memorial Sloan Kettering Cancer Center have examined the Newcastle disease virus, which is an RNA virus that is a part of the Paramyxoviridae family that primarily affects birds and poses no threat to human health. Additionally, Newcastle disease virus has a predilection for cancer cells while sparing normal cells, Kahn adds. Newcastle disease virus has shown early promise in animal studies and human trials in melanoma, and investigators are aiming to see if it could also be effective in ovarian cancer, Kahn notes.

The rationale for encoding IL-12 with the Newcastle disease virus is that IL-12 promotes maturation of T cells and Th1 cells, and helps with upregulation of antigen-presenting cells, Kahn says. In preclinical mouse models, intraperitoneal therapy with Newcastle disease virus encoded with IL-12 caused an increase in activated T-cell infiltration in both treated peritoneal tumors and untreated distant tumors, and it favorably modified the ovarian tumor microenvironment.

The next steps for evaluating Newcastle disease virus encoded with IL-12 in ovarian cancer could involve testing it in combination with an anti–PD-L1 agent, or in combination or comparison with conventional systemic therapy, potentially followed by in-human clinical trials.

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Ryan Kahn, MD, MHS, discusses the investigation of Newcastle disease virus encoded with interleukin 12 in ovarian cancer.

Dr Kahn on the Investigation of Newcastle Disease Virus With IL-12 in Ovarian Cancer

Widespread germline testing in the United States could prevent cancer in hundreds of thousands of people. However, despite known benefits, uptake for genetic testing has been slow: only 1 in 5 individuals use recommended genetic services even when there is a significant family history of colorectal, breast, or ovarian cancer.

The most commonly cited barriers to testing are lack of awareness, difficulty of access, and cost.

 Early detection of hereditary cancers and subsequent medical or surgical intervention decreases mortality, therefore this missed opportunity means an immense loss of lives.

Cascade testing identifies individuals who unknowingly carry pathogenic variants in cancer-susceptibility genes through familial diffusion of genetic risk information. Once a patient receives a diagnosis, genetic testing can be extended to at-risk relatives so that those who carry the familial pathogenic variant can take advantage of cancer surveillance and disease-reducing surgery.

Approximately 10 million women in the US without a personal history of cancer are at risk of carrying a cancer-susceptibility mutation have not undergone genetic testing. A 2020 study projected that widespread peri-diagnostic cascade testing in the US with an uptake rate of 70% had the potential to achieve population-wide identification of all susceptibility mutations within 10 years.

As long ago as 2014, the CDC designated cascade testing a tier 1 genetic application for hereditary breast, ovarian, and nonpolyposis colorectal cancer (Lynch syndrome).

 But its promise will be realized only when the barriers to testing have been eliminated. Because one of the biggest is lack of awareness, we developed a website to address it, with support from our principal investigator–Melissa Frey, MD, assistant professor of gynecologic oncology at Weill Cornell Medicine–and funding from the Foundation for Women’s Cancer and the Perlman Family CCARE Lynch Syndrome Research Foundation.

Providing Resources for Patients and Physicians 

A free portal, CascadeResources.net lists entities that provide cancer screening guidelines, genetic testing, variant interpretation, counseling, financial assistance, and support forums. The Network is a nonprofit, independently run organization unaffiliated with any of the entities listed or linked to on the site. 

As gynecologic oncology fellows, we focus on surgery, medical oncology, and clinical medicine. So when it came to developing the portal, we turned to the website building and hosting company Squarespace, which made the process much easier for us novices. 

Since our launch in October 2021, monthly page visits have steadily increased, and the network continues to expand. As more organizations discover us and ask to be included, we will be able to provide additional resources. 

New members have also joined the team: Hannah Bergeron and Muhammad Danyal Ahsan, research assistants at Weill Cornell Medicine, and Emily H. Miller, MD, MPH, an OB-GYN resident at NewYork- Presbyterian Weill Cornell.

We are building a page to help patients and providers navigate ClinicalTrials.gov when searching for trials of specific pathogenic variants, and developing instructional videos for physicians on how to discuss cascade genetic testing with patients and their relatives. To increase the Network’s visibility and scope, we are collaborating with news and research outlets and investigating search engine optimization. 

CascadeResources.net has been a fulfilling project and one that we hope will continue to be of use for patients, their families, and health care providers.

Offit K, Tkachuk KA, Stadler ZK, et al. Cascading after peridiagnostic cancer genetic testing: an alternative to population-based screening. 

2020;38(13):1398-1408.doi:10.1200/JCO.19.02010

Finch APM, Lubinski J, Møller P, et al: Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. 

2014;32(15):1547-1553 doi:10.1200/JCO.2013.53.2820

Frey MK, Kahn RM, Chapman-Davis E, et al. Prospective feasibility trial of a novel strategy of facilitated cascade genetic testing using telephone counseling. 

 2020;38(13):1389-1397. doi:10.1200/JCO.19.02005

Centers for Disease Control and Prevention. Tier 1 genomics applications and their importance to public health. March 6, 2014. Accessed January 21, 2022. bit.ly/3Ioet2n

Ryan M. Kahn, MD, MHS

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Dr Kahn on the Investigation of Newcastle Disease Virus With IL-12 in Ovarian Cancer

Two Fellows Use Online Resources to Boost Genetic Testing