Cancer vaccines show promise for treatment and prevention
· Medical Xpressedited by Lisa Lock, reviewed by Robert Egan
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For more than three decades, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center researchers have pursued an ambitious idea: that vaccines could train the immune system to recognize and fight cancer. Now, a landmark phase 3 clinical trial of a personalized melanoma vaccine shows that this approach can improve outcomes for patients. Johns Hopkins Kimmel Cancer Center was among the clinical centers that participated in the multicenter study.
"Vaccines have been among the most transformative advances in modern medicine," says Mark Yarchoan, M.D., associate professor of oncology, in an editorial published Nov. 11 in the New England Journal of Medicine, accompanying the melanoma trial results. "However, until now, efforts to develop vaccines that directly target established cancers have been largely unsuccessful."
The clinical trial results mark a turning point for a field shaped by decades of fundamental discoveries and many clinical setbacks. Among its pioneers is Elizabeth Jaffee, M.D., the Dana and Albert "Cubby" Broccoli Professor of Oncology and deputy director of the Johns Hopkins Kimmel Cancer Center, whose work helped establish therapeutic cancer vaccination as a promising strategy to fight cancer.
"For years, we believed we could teach the immune system to recognize cancer, but we didn't yet have all of the tools to make this work in patients," says Jaffee, who is also co-director of the Kimmel Cancer Center's Skip Viragh Center for Pancreatic Cancer and associate director of its Bloomberg~Kimmel Institute for Cancer Immunotherapy. "These results reflect decades of work by many scientists and patients who kept pushing the field forward, even when early clinical trials were disappointing."
Early vaccines meet checkpoint immunotherapy
In the late 1980s, Jaffee and other Johns Hopkins Sidney Kimmel Comprehensive Cancer Center immunologists helped pioneer therapeutic cancer vaccines. Jaffee and Daniel Laheru, M.D., the Ian T. MacMillan Professor in Clinical Pancreatic Cancer and co-director of the Skip Viragh Center for Pancreatic Cancer, brought the approach into early clinical trials for pancreatic cancer. Their GVAX vaccine used genetically modified tumor cells to stimulate an immune response against cancer. Later studies demonstrated that vaccination could generate organized clusters of immune cells within pancreatic tumors, long considered among the hardest cancers for the immune system to attack.
Other breakthroughs at Johns Hopkins Medicine helped explain why cancer vaccines might work better when combined with immunotherapy. Research by Johns Hopkins Kimmel Cancer Center and Bloomberg~Kimmel Institute for Cancer Immunotherapy scientists, including Drew Pardoll, M.D., Ph.D., Suzanne Topalian, M.D., and Julie Brahmer, M.D., helped advance PD-1 checkpoint inhibitors, drugs that release the brakes on the immune system and are now being combined with cancer vaccines.
Tumor mutations guide personalized vaccines
At the same time, advances in cancer genetics and immunology helped identify what cancer-fighting T cells should attack. Building on pioneering cancer genetics research at the Ludwig Center at Johns Hopkins, Bert Vogelstein, M.D., Clayton Professor of Oncology and Howard Hughes Medical Institute investigator, and Kenneth Kinzler, Ph.D., Barry Family Professor of Oncology, helped demonstrate the importance of genetic mutations in determining which cancers respond to immunotherapy.
Studies led by Dung Le, M.D., Bloomberg~Kimmel Professor of Cancer Immunotherapy, and former Kimmel Cancer Center faculty member Luis Diaz, M.D., linked defects in DNA mismatch repair (DNA copying errors that cause high rates of mutations) to responses to PD-1 blockade. Subsequent research at the Johns Hopkins Kimmel Cancer Center showed that PD-1 therapy can expand T cells that recognize mutation-associated neoantigens, proteins created by mutations found in cancer cells but not healthy tissue.
Together, these discoveries helped establish the rationale behind today's personalized cancer vaccines: identify the distinctive mutations in a patient's tumor, vaccinate against them to stimulate cancer-specific T cells and use checkpoint blockade to help those immune cells remain active. In 2016, the Bloomberg~Kimmel Institute for Cancer Immunotherapy brought researchers working on vaccines, immunotherapies, tumor genetics and clinical trials into closer collaboration.
Extending vaccines to liver cancer
Johns Hopkins Kimmel Cancer Center researchers are already developing cancer vaccines that aim to extend this approach to other tumor types and earlier stages of disease. In a 2024 study led by Yarchoan, a personalized vaccine combined with the immunotherapy drug pembrolizumab showed encouraging activity in hepatocellular carcinoma, the most common form of liver cancer.
A separate Johns Hopkins-led vaccine trial conducted by Yarchoan and Marina Baretti, M.D., the Jiasheng Professor in Hepato-Biliary Cancer Research, showed responses in fibrolamellar carcinoma, a rare liver cancer that affects adolescents and young adults.
Testing pancreatic cancer prevention
Building on decades of pioneering cancer vaccine research, Jaffee and Neeha Zaidi, M.D., associate professor of oncology, are leading clinical studies of an experimental vaccine targeting mutations in KRAS, a gene altered in more than 90% of pancreatic cancers. KRAS mutations can occur a decade or more before pancreatic cancer develops, so they offer an opportunity to train the immune system to recognize and attack abnormal cells before they become cancer.
In a recent study involving 20 people at elevated risk for pancreatic cancer, the vaccine was safe and generated significant immune responses in 90% of participants, with cancer-fighting immune cells detectable for up to two years. None developed pancreatic cancer during the follow-up period, although larger studies with longer follow-up are needed to determine whether the vaccine can prevent the disease.
Additional studies are exploring whether the vaccine can prevent certain pancreatic cysts from progressing to cancer and whether combining the vaccine with other immunotherapies can improve treatment for patients who already have pancreatic cancer.
Yarchoan says the emerging evidence suggests cancer vaccines may ultimately have applications across multiple cancer types, but realizing their full potential will require ambitious clinical trials and sustained research investment.
Publication details
Mark Yarchoan, Cancer Vaccines — From Treatment to Prevention, New England Journal of Medicine (2026). DOI: 10.1056/nejme2614041
Journal information: New England Journal of Medicine
Key medical concepts
Pancreatic CancerInhibitor, PD-1
Clinical categories
OncologyAllergy and immunology Provided by Johns Hopkins University Who's behind this story?
Lisa Lock
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