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More than two decades ago, a small group of women with advanced breast cancer took part in a clinical trial that tested an experimental vaccine. All these years later, every one of them is still alive. Researchers say survival over such a long period is extremely uncommon for people with metastatic breast cancer, which is why the case drew renewed scientific attention.
Researchers at Duke Health took a closer look at the immune systems of the women who participated in the trial, which was led by Herbert Kim Lyerly, M.D., George Barth Geller Distinguished Professor of Immunology at Duke University School of Medicine. What they discovered surprised them. Even after many years, the women still had powerful immune cells that could recognize their cancer.
These immune cells shared a specific marker known as CD27. This marker plays an important role in helping the immune system remember past threats and respond to them again. The results, published in Science Immunology, point to CD27 as a possible way to make cancer vaccines far more effective.
"We were stunned to see such durable immune responses so many years later," said Zachary Hartman, Ph.D., senior author of the study and associate professor in the Departments of Surgery, Integrative Immunology and Pathologyat Duke University School of Medicine. "It made us ask: What if we could boost this response even more?"
Testing the CD27 Approach in the Lab
To explore that question, the research team ran experiments using mice. They combined a vaccine aimed at HER2 (a protein on the surface of some cells, including breast cancer) with an antibody designed to activate CD27. The results were striking. Nearly 40% of mice that received the combined treatment saw their tumors disappear completely. By comparison, only 6% of mice treated with the vaccine alone experienced the same outcome.
Further analysis showed that the CD27 antibody worked by greatly enhancing the activity of CD4+ T cells, a type of immune cell.
A Bigger Role for Overlooked Immune Cells
According to Hartman, CD4+ T cells, often called "helper" cells, do not usually get much attention in cancer research. Most studies focus instead on CD8+ "killer" T cells, which are known for directly attacking tumors. This study suggests the helper cells may be just as important. They appear to drive lasting immune memory and support other immune cells so they can work more effectively.
When researchers added another antibody that further supports CD8+ T cells, tumor rejection rates in mice climbed to nearly 90%.
"This study really shifts our thinking," Hartman said. "It shows that CD4+ T cells aren't just supporting actors; they can be powerful cancer fighters in their own right and are possibly essential for truly effective anti-tumor responses."
Implications for Future Cancer Treatments
The team also discovered that the CD27 antibody only needed to be given once, at the same time as the vaccine, to produce long lasting effects. This simplicity could make it easier to pair the approach with existing cancer treatments, including immune checkpoint inhibitors and antibody-drug conjugates already used in patients.
Hartman believes these findings may help cancer vaccines finally reach their full promise.
"We've known for a long time that vaccines can work against cancer, but they haven't lived up to the hype," he said. "This could be a missing piece of the puzzle."
The study received funding from the National Institutes of Health (117 R01CA238217-01A1/02S1) and the Department of Defense (W81XWH-20-1-034618 and W81XWH-21-2-0031).
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