A 20-year-old cancer vaccine may hold the key to long-term survival
Duke Health
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 Pathology at 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).
- Bin-Jin Hwang, Erika J. Crosby, David T. Severson, Timothy N. Trotter, Jason McBane, Li-Chung Tsao, Tao Wang, Cong-Xiao Liu, Xiao-Yi Yang, Gangjun Lei, Junping Wei, Xingru Ma, Bushanqing Liu, Amy Hobeika, Michael Morse, Jesuchristopher Joseph, Ethan Agritelley, Elishama Kanu, Karrie Comatas, Tibor Keler, Li-Zhen He, Herbert Kim Lyerly, Zachary C. Hartman. CD27 agonism enhances long-lived CD4 T cell vaccine responses critical for antitumor immunity. Science Immunology, 2025; 10 (114) DOI: 10.1126/sciimmunol.adz2294
