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

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.