Lynch Syndrome: Cancer Vaccine Shows Promise

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Investigational Vaccine NOUS-209 Shows Promise in Preventing Cancer in High-Risk Individuals with Lynch Syndrome

A new cancer vaccine, NOUS-209, is demonstrating the potential to intercept and eliminate precancerous and cancerous cells in individuals with Lynch syndrome, offering a potential path to cancer prevention for this high-risk population. The encouraging findings, published in nature medicine, stem from a phase Ib/II clinical trial.

Current strategies for managing Lynch syndrome – frequent cancer screenings or proactive, preventative surgery – are effective but can considerably impact a patient’s quality of life.”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,” explained a lead researcher from The University of Texas MD Anderson Cancer Center.

did you know? – Lynch syndrome, formerly known as hereditary nonpolyposis colorectal cancer (HNPCC), is the most common inherited cancer syndrome. It accounts for approximately 3-5% of all colorectal cancers.

Understanding Lynch Syndrome and the Need for Innovation

lynch syndrome is an inherited disorder caused by genetic mutations affecting DNA mismatch repair. These mutations occur in approximately one in every 300 individuals, dramatically increasing their lifetime cancer risk – up to 80% – and frequently enough leading to earlier cancer onset. The syndrome predisposes individuals to a range of cancers, including colorectal, endometrial, and urothelial cancers.

Reader question – Neoantigens are unique mutations found on cancer cells. NOUS-209 targets these, allowing the immune system to specifically attack cancerous cells while sparing healthy tissue.

How NOUS-209 works: A neoantigen-Directed approach

NOUS-209 is a novel neoantigen-directed cancer vaccine.It utilizes a combination of a great ape adenovirus and modified vaccinia virus ankara to deliver 209 frameshift peptides – unique markers found on cells with microsatellite instability, a hallmark of many cancers associated with Lynch syndrome.The vaccine essentially trains the immune system to identify and destroy cells displaying these frameshift peptides.

Researchers conducted a phase Ib/II, single-arm trial to assess the vaccine’s safety and ability to stimulate an immune response in individuals with Lynch syndrome. The initial cohort comprised 45 participants evaluated for both safety and immunogenicity.

Key Findings: Safety and Robust Immune Response

The trial demonstrated a favorable safety profile, with no serious adverse events linked to the vaccine. The most commonly reported side effects were injection-site reactions – experienced by 91% of participants after the initial dose and 76% after the booster – and fatigue,reported by 80% and 53% respectively. Importantly, no grade 3 injection-site reactions were observed.

Remarkably, 100% of the 37 participants whose data was evaluable exhibited observable neoantigen-specific immune responses and strong T cell immunity following vaccination. Furthermore, 85% of participants maintained a durable immune response at the one-year mark.

The vaccine successfully induced both CD8-positive and CD4-positive T cells, enabling them to recognize multiple frameshift peptides. In laboratory tests, over 100 immunogenic frameshift peptides were identified and shown to have cytotoxic activity – meaning they were able to kill cancer cells.

Looking Ahead: Cancer Interception with NOUS-209

The study authors are optimistic that these early results warrant continued development of NOUS-209 as a strategy for cancer interception – stopping cancer before it develops or progresses.

The research was sponsored by nouscom, the National Cancer Institute, and MD Anderson’s iCAN-PREVENT consortium.Full disclosures regarding the study authors can be found at nature.