Scientists Pursue Cancer Vaccines Tailored to the Genetic Makeup of an Individual's Tumor

"The Royal Swedish Academy of Sciences, which selects Nobel laureates in chemistry and physics, last week awarded Dr. Wu its Sjoberg Prize in honor of 'decisive contributions' to cancer research," reports CNN. Their profile of the oncologist from Boston's Dana-Farber Cancer Institute notes Dr. Wu's research "has laid the scientific foundation for the development of cancer vaccines tailored to the genetic makeup of an individual's tumor."It's a strategy looking increasingly promising for some hard-to-treat cancers such as melanoma and pancreatic cancer, according to the results of early-stage trials, and may ultimately be widely applicable to many of the 200 or so forms of cancer... The most common treatments for cancer - radiation therapy and chemotherapy - are like sledgehammers, striking all cells and often damaging healthy tissue. Since the 1950s, cancer researchers have been seeking a way to dial up the body's immune system, which naturally tries to fight cancer but is outsmarted by it, to attack tumor cells. Progress on that front was middling until about 2011 with the arrival of a class of drugs called checkpoint inhibitors, which boost the anti-tumor activity of T cells, an important part of the immune system... These drugs have helped some people with cancer who would have been given months to live survive for decades, but they don't work for all cancer patients, and researchers continue to look for ways to turbocharge the body's immune system against cancer... Wu's research focused on small mutations in cancer tumor cells. These mutations, which occur as the tumor grows, create proteins that are slightly different to those in healthy cells. The altered protein generates what's called a tumor neoantigen that can be recognized by the immune system's T cells as foreign, and therefore susceptible to attack. With thousands of potential neoantigen candidates, Wu used "tour de force lab work" to identify the neoantigens that are on the cell surface, making them a potential target for a vaccine, said Urban Lendahl, professor of genetics at the Karolinska Institutet in Sweden and the secretary of the committee that awarded the prize. "If the immune system is to have a chance to attack the tumor, this difference must be manifested on the surface of the tumor cells. Otherwise, it's pretty pointless," Lendahl added... By sequencing DNA from healthy and cancer cells, Wu and her team identified a cancer patient's unique tumor neoantigens. Synthetic copies of these unique neoantigens could be used as a personalized vaccine to activate the immune system to target the cancer cells... Once it had FDA approval, the team vaccinated six patients with advanced melanoma with a seven-shot course of patient-specific neoantigens vaccines. The breakthrough results were published in an 2017 article in Nature. For some patients, this treatment resulted in the immune system's cells being activated and targeting the tumor cells. The results, along with another paper published the same year led by the founders of mRNA vaccine company BioNTech, provided "proof of principle" that a vaccine can be targeted to a person's specific tumor, Lendahl said. A follow-up by Wu's team four years after the patients received the vaccines published in 2021, showed that the immune responses were effective in keeping cancer cells under control... Since then, Wu's team, other groups of medical researchers and pharmaceutical companies, including Merck, Moderna and BioNTech, have further developed this field of research, with trials underway for vaccines that treat pancreatic and lung cancer as well as melanoma. "All the trials underway are small-scale, typically involving a handful of patients with later-stage disease and a high tolerance for safety risks," adds CNN. "To show that these type of cancer vaccines work, much larger randomized control trials are needed."

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