Researchers at the Perelman School of Medicine and the Abramson Cancer Center at the University of Pennsylvania report that a short course of vaccination with an anti-HER2 dendritic cell vaccine made partly from the patient’s own cells triggers a complete tumor eradication in nearly 20 percent of women with ductal carcinoma in situ (DCIS), an early breast cancer.
“I think these data more than prove that vaccination works in situations where the target is right,” says the study’s leader, Brian Czerniecki, MD, PhD, surgical director of the Rena Rowan Breast Center and Surgical Director of the Immunotherapy Program for the Abramson Cancer Center. “Previous vaccines targeted tissue antigens that were expressed on the cancer cells, but were not necessary for tumor survival. So a vaccine response would cause the tumor to just stop expressing the antigen and the tumor would be fine. Here we’re going after HER2/neu, which is critical for survival of early breast cancers. If we knock it out with the immune response, we cripple the tumor cells.”
Czerniecki and colleagues enrolled 27 women with HER2-positive DCIS. They isolated specialized white cells from the patients’ blood using standard apheresis techniques similar to the blood donation process. Once isolated, the researchers activated the dendritic cells, which are key regulators of the immune system, and primed them with small pieces of the HER2/neu protein in Penn’s Clinical Cell and Vaccine Production Facility. Each patient then received four shots, one week apart, of their personalized anti-HER2 vaccine. And two weeks later patients had surgery to remove any remaining disease, which is standard care for DCIS patients.
The new approach has several critical advantages, compared to testing a vaccine in patients with more advanced disease. First, the activated immune cells have fewer tumor cells to kill. Second, patients’ immune systems are still responsive, unlike advanced cancer patients whose immune systems have been suppressed by their disease. Third, the investigators are able to see results quickly, by looking at serum and tumor biomarkers.
In fact, when the team compared pre-vaccination biopsy samples with post-vaccination surgical samples, they saw dramatic changes: Five patients had no disease visible at the time of surgery, indicating that their immune system had wiped out the tumor. Of the remaining 22 patients, HER2 expression was eliminated in half (11 patients), and reduced by 20 percent or more in another two. “We are continuing to see this pattern in our second, ongoing trial,” Czerniecki says.
When the team looked at immune responses, they found that 85 percent of patients had HER2-reactive CD4 and CD8 T cells, suggesting that the patients developed a robust and relatively complete immune response after vaccination. Importantly, some patients maintained their immune responses as long as 52 months, which means that they continue to have some protection from recurrence of HER2-positive disease – a key insurance policy for patients, since doctors currently are unable to accurately predict which women are likely to develop invasive breast cancer following a DCIS diagnosis.
The results of the study show the vaccine is safe and relatively easy for the women, with only low-grade side effects. The most common side effects were malaise (72 percent), injection site soreness (59 percent), chills or rigors (38 percent), fever (28 percent) and headaches (24 percent).
While the numbers of patients treated in the trial are relatively small, Czerniecki thinks they will have some idea whether the vaccination reduces the risk of disease recurrence within the next two years. In the meantime, the team continues enrolling patients in a larger study, is designing another study to test the approach in women with early invasive breast cancer, and also plans to test vaccination with additional antigens, including HER3 and HER1.
“I think if we target several of the HER2 family members, we’ll drive the tumor to a place where it has nowhere to go,” Czerniecki says. “Basically, we’ll push it over a cliff because those pathways are critical for tumor survival.”
Czerniecki notes that what the team is learning in DCIS is applicable to invasive breast cancer, and to other solid tumors that rely on the HER family of signaling proteins, including melanoma, lung, brain, and colon cancers.
Co-authors include Anupama Sharma, MD, Ursula Koldovsky, PhD, Shuwen Xu, MD, Rosemarie Mick, MS, Robert Roses, MD, Elizabeth Fitzpatrick, BS, Susan Weinstein, MD, Harvey Nisenbaum, MD, Bruce L. Levine, MD, Kevin Fox, MD, and Paul Zhang, MD, PhD from Penn, and Gary Koski, PhD, from Kent State University in Ohio.
This study was funded by an NIH grant (R01 CA096997), the Harrington Foundation, Pennies in Action, and the Mistler Foundation.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.
Penn's Perelman School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.
Holly Auer | EurekAlert!
Microgel powder fights infection and helps wounds heal
14.11.2018 | Michigan Technological University
Spread of deadly eye cancer halted in cells and animals
13.11.2018 | Johns Hopkins Medicine
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
16.11.2018 | Physics and Astronomy
16.11.2018 | Physics and Astronomy
16.11.2018 | Life Sciences