Investigational Cancer Vaccine Intercepts Cells in Lynch Syndrome Carriers

An investigational cancer vaccine, NOUS-209, has shown potential for intercepting precancerous and cancerous cells before the disease can develop in individuals with Lynch syndrome, thereby showing the potential to prevent cancer from developing in these high-risk individuals, according to findings from a phase Ib/II trial published in Nature Medicine. "Current management strategies for Lynch Syndrome patients—frequent screenings or elective preventive surgery—are life-changing interventions that help prevent cancer development but can significantly affect quality of life," said principal investigator Eduardo Vilar-Sanchez, MD, PhD, Chair Ad Interim of Clinical Cancer Prevention at The University of Texas MD Anderson Cancer Center. "By teaching the immune system to recognize and attack abnormal cells, this therapy offers a promising new approach to this patient population, who face a significantly higher risk of colorectal, endometrial, urothelial, and other cancers." Background and Study Methods Lynch syndrome is a hereditary cancer syndrome caused by germline mutations in DNA mismatch repair genes that can be found in about one in every 300 individuals, which increases their overall lifetime cancer risk to up to 80% and often results in younger onset of cancer development, according to researchers. Nous-209 is a neoantigen-directed cancer vaccine made with great ape adenovirus and modified vaccinia virus Ankara that encodes 209 frameshift peptides that are shared through microsatellite instability neoplasms. Investigators conducted a phase Ib/II single-arm trial to explore the use of Nous-209 to intercept cancer in individuals with Lynch syndrome. Cohort one of the study included 45 participants assessed for safety and immunogenicity. Key Findings Vaccination was found to be safe, and no intervention-related serious adverse events were reported. Injection-site reactions (any grade, 91% after prime, 76% after boost) and fatigue (any grade, 80% after prime, 53% after boost) were the most common adverse events, and there were no grade 3 injection-site reactions observed. After vaccination, 100% of 37 evaluable participants had observable neoantigen-specific immune responses and potent T cell immunity. At 1 year, 85% of participants had a durable immune response. CD8-positive and CD4-positive T cells were both induced and able to recognize multiple frameshift peptides. More than 100 immunogenic frameshift peptides were identified and tested in vitro for cytotoxic activity. The study authors believe these early results support further development for Nous-209 for cancer interception.