Dr. Lipkin on Cancer Prevention Vaccine in Preclinical Model of Lynch Syndrome

Steven M. Lipkin, MD, PhD, the Gladys and Roland Harriman Professor of Medicine, professor of medicine in the Division of Gastroenterology and Hepatology, vice chair for Research of the Department of Medicine at Weill Cornell Medicine; and a geneticist at NewYork-Presbyterian/Weill Cornell Medical Center, discusses a study of a cancer prevention vaccine in a preclinical model of Lynch syndrome during the 2019 AACR Annual Meeting.

Investigators evaluated a neoantigen vaccine in mice models who had developed Lynch syndrome to determine the safety and efficacy prior to testing it in humans. The key concept is that mutation rates of Lynch syndrome are so high that patients develop precisely the same mutations that occur across tumors, Lipkin explains.

The vaccination with as few as 4 tumor antigens generated antigen-specific responses, reduced intestinal tumors, and improved survival in the mouse model. Moreover, the combination of the vaccination and naproxen significantly improved overall survival for mice with Lynch syndrome versus vaccination alone. The overall survival was 541 days compared with 380 days in mice that only were treated with the vaccine.

Investigators envision a system where, going forward, there will be a library of peptides and a preliminary analysis of a patient's immune background would be conducted. Peptides would then be mixed with adjuvants that stimulate the immune system, causing T cells to attack. Next steps following this research, Lipkin says, includes identifying an optimal system of peptides, which adjuvant to use, and how many injections should be administered. Then, researchers will conduct a first-in-human study to evaluate safety and whether the immune systems are activated against these mutations.

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