Oct. 18, 2025
Despite declining tobacco use, lung cancer remains the leading cause of cancer-related death worldwide. As oncologists seek more-effective and individualized therapies, Mayo Clinic researchers are advancing a promising frontier: cancer vaccines. These immunotherapies are designed not only to treat existing disease but also to prevent recurrence and, potentially, primary onset in high-risk populations.
Keith L. Knutson, Ph.D., an immunologist and cancer vaccine researcher at Mayo Clinic in Florida, is leading efforts to develop both therapeutic and preventive vaccines for lung cancer.
"A cancer vaccine is similar to an infectious disease vaccine," says Dr. Knutson. "It's a medicine we give to stimulate the immune system with antigens derived from cancer."
These antigens can be used to train the immune system to recognize and destroy cancer cells.
Therapeutic vaccines: Targeting the individual tumor
Unlike traditional therapies, therapeutic cancer vaccines are tailored to the unique genetic makeup of a patient's tumor. "Because cancer grows so rapidly, there are lots of defects in cancer cells," Dr. Knutson explains. "The cells don't repair their DNA or RNA well enough, and they accumulate mutations." These mutations serve as distinct targets for vaccine development.
Mayo Clinic's approach involves sequencing tumor DNA and RNA obtained via biopsy to create a personalized vaccine. This individualized strategy is being explored for two primary applications: preventing recurrence and reducing metastatic spread.
"Even when the tumor is gone, patients have a high risk of their cancer coming back," Dr. Knutson says. "After conventional therapies, we can train the immune system to prevent that type of cancer from returning. The hope is that the cells we stimulate with vaccines can recognize and seek out cancer and destroy it before it becomes a problem."
In advanced cases, researchers are investigating whether the immune system can be stimulated to generate sufficient T cells to locate and attack tumors throughout the body.
Preventive vaccines: Expanding the scope
Beyond personalized treatment, Mayo Clinic is also developing a preventive vaccine targeting common oncogenes found in breast and lung cancers. This vaccine includes antigens for HER2 and MUC1, proteins overexpressed in a significant percentage of non-small cell lung cancers (NSCLCs).
HER2, which regulates cell growth and division, is overexpressed in approximately 13% to 20% of NSCLCs. MUC1, another target, is found in up to 80% of NSCLCs.
"HER2, for example, is also overexpressed in ovarian cancer," Dr. Knutson says. "So, if we had a vaccine that prevented breast and lung cancers by targeting HER2, it has the potential to treat or prevent other types of cancer with that overexpression."
This preventive strategy could be particularly valuable for patients with a strong family history or genetic predisposition to HER2-positive cancers. It also opens the door to broader applications of vaccine technology across multiple cancer types.
Implications for clinical practice
For cancer clinicians, these developments represent a shift toward precision immunotherapy that could complement existing treatment protocols. While these vaccines are still in clinical development, they offer hope for patients with limited options and high recurrence risk.
"Fifty years ago, we didn't have the capabilities we have now," Dr. Knutson reflects. "Our capabilities are rapidly changing and accumulating. Over the next 20 years, we're going to see some great improvements in how we use vaccines to activate the immune system to suppress cancer development, treat cancer and prevent it from coming back."
As vaccine-based therapies continue to evolve, collaboration between researchers and clinicians will be key to translating these innovations into improved patient outcomes.
For more information
Based on Saenz J. Vaccines: The next frontier of lung cancer treatment and prevention. Mayo Clinic.
Refer a patient to Mayo Clinic.