A group of women with advanced breast cancer who participated in a clinical trial more than two decades ago are still alive, an outcome described as rare for patients with metastatic breast cancer. The long-term survival of these women has drawn the attention of researchers at Duke Health.
The original trial was led by Herbert Kim Lyerly, M.D., George Barth Geller Distinguished Professor of Immunology at Duke University School of Medicine. Scientists have now studied the immune systems of these participants and found that they still possess strong immune cells capable of recognizing their cancer after many years.
These immune cells display a marker known as CD27, which is important for helping the immune system remember and respond to threats such as cancer. The findings were published in Science Immunology on October 28.
“We were stunned to see such durable immune responses so many years later,” said Zachary Hartman, Ph.D., senior author and associate professor in the Departments of Surgery, Integrative Immunology and Pathology at Duke University School of Medicine. “It made us ask: What if we could boost this response even more?”
To investigate further, researchers tested a stimulatory antibody targeting CD27 alongside a vaccine aimed at HER2—a protein present on some breast cancer cells—in several mouse models. Results showed that nearly 40% of mice receiving both treatments experienced complete tumor regression, compared to only 6% with the vaccine alone.
The study revealed that the antibody enhanced the activity of CD4+ T cells, a type often overlooked in favor of CD8+ T cells in cancer research. Hartman explained that these “helper” CD4+ cells play a central role in establishing long-term immune memory and supporting other immune functions.
“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.”
When another antibody designed to aid CD8+ T cells was added to the treatment regimen, tumor rejection rates improved further in mice—reaching nearly 90%.
Researchers also noted that administering the CD27 antibody just once alongside the vaccine was sufficient for lasting effects. This approach may allow easier integration with current cancer therapies such as immune checkpoint inhibitors and antibody-drug conjugates already used clinically.
Hartman stated: “We’ve known for a long time that vaccines can work against cancer, but they haven’t lived up to the hype. This could be a missing piece of the puzzle.”
The study received funding from both the National Institutes of Health and the Department of Defense.
Duke University Hospital is located in Durham, North Carolina, and was established in 1925. It serves as both a treatment center—with over 41,000 patient admissions reported in its most recent annual report—and as a training hospital under President Craig T. Albanese (https://www.dukehealth.org/hospitals/duke-university-hospital).
