Gastroenterology, Oncology

Moving the Needle Toward a Vaccine for Cancers Associated with Lynch Syndrome

    NewYork-Presbyterian/Weill Cornell Medicine doctors are harnessing the ribonucleic acid (RNA) vaccine technology that was so successful during the COVID-19 pandemic to help advance efforts to deliver a vaccine for cancers associated with Lynch syndrome. Steven M. Lipkin, MD, PhD, FACMG, a medical geneticist focused on hereditary gastrointestinal cancer syndromes at NewYork-Presbyterian/Weill Cornell Medicine, is currently conducting experiments in mice to determine the best vaccine cargo for an RNA vaccine targeted for Lynch syndrome.

    Lynch syndrome affects one in every 280 Americans, or approximately one million people. It is an inherited condition that confers a predisposition for certain cancers, including colorectal, endometrial, and stomach cancer. An individual with Lynch syndrome could have a lifetime risk as high as 70% for these cancers. There is no cure for Lynch syndrome, and it is typically managed through evidence-based cancer prevention strategies, such as aspirin use and screening colonoscopies in colorectal cancer.

    digital illustration explaining Lynch syndrome

    Lynch syndrome affects one in every 280 Americans, or approximately one million people.

    Genetic Mutations Serve as Target for Potential Vaccine

    The concept of creating a vaccine for Lynch syndrome associated cancers is promising because of the syndrome’s pattern of genetic mutations. “In Lynch syndrome there are very high mutation rates, but they are not random. They occur in particular, repetitive sequences resulting in hundreds of genes that recurrently mutated. Because you have recurrent mutations, you have something that you can put into a vaccine that makes it more feasible,” says Dr. Lipkin.

    In Lynch syndrome there are very high mutation rates, but they are not random.

    — Dr. Steven Lipkin

    In previous preclinical research, Dr. Lipkin and his colleagues were able to use as few as four of the recurrent mutations to create a peptide-based vaccine that inhibited cancer and prolonged overall survival in a mouse model of Lynch syndrome. Now they are seeking to adapt that model using RNA vaccine technology and then to test the two types of vaccines head-to-head in mouse models.

    The RNA technology has a lot of promise to potentially optimize vaccine delivery in Lynch syndrome. “The ability to get the immune system activated by the RNA vaccines is greater than any vaccine technology we’ve ever seen before,” says Dr. Lipkin. “It’s much more powerful in terms of its ability to awaken the immune system to cancer mutations.”

    digital illustration of intestinal carcinoma, colorectal cancer, bowel neoplasia

    A Lynch syndrome vaccine could be used alone or with colonoscopy to prevent colorectal cancer.

    The Lynch syndrome vaccine research is one of four ongoing cancer prevention projects that are part of the Weill Cornell Medicine CAP-IT Center for LNP RNA Immunoprevention. In 2022, the Center received a five-year, $5.7 million grant from the National Cancer Institute, part of the National Institutes of Health, to explore the development of liponanoparticle (LNP) RNA vaccines for precision prevention of individuals with increased cancer risk.

    “The risk of dying from cancer is about 20% lower than it was just 20 years ago, and a lot of that benefit is not from the sexy things like immunotherapy, but from prevention,” says Dr. Lipkin. “Specifically, it’s from reducing smoking, vaccinating people against viral cancers like the human papillomavirus, and vaccinating against Hepatitis B and C. We think that the next big thing to reduce cancer risk is going to be vaccines.”

    We think that the next big thing to reduce cancer risk is going to be vaccines.

    — Dr. Steven Lipkin

    If a successful Lynch syndrome vaccine is developed, it could be used as a standalone prevention strategy or in combination with other approaches such as colonoscopy, explains Dr. Lipkin.

    The applications of a Lynch syndrome vaccine likely won’t stop with patients who have a genetic predisposition putting them at higher risk for developing cancer. Instead, a Lynch syndrome vaccine could offer a roadmap for creating a cancer vaccine for the general public. “If you suppose it takes a hundred different steps to produce a cancer vaccine, we could get 95 of them right with Lynch syndrome and then adapt it for people who are at average risk for cancer,” says Dr. Lipkin.

      Learn More

      Sei S, Ahadova A, Keskin DB, et al. Lynch syndrome cancer vaccines: A roadmap for the development of precision immunoprevention strategies. Front Oncol. 2023;13:1147590. Published 2023 Mar 22. doi:10.3389/fonc.2023.1147590.

      Gebert J, Gelincik O, Oezcan-Wahlbrink M, et al. Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity With Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model [published correction appears in Gastroenterology. 2021 Dec;161(6):2070]. Gastroenterology. 2021;161(4):1288-1302.e13. doi:10.1053/j.gastro.2021.06.073.

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