Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Four-Week Vaccination Regimen Knocks Out Early Breast Cancer Tumors, Penn Researchers Report

31.01.2012
Majority of Patients Treated Develop Strong, Lasting Immune Responses

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.

More than 85 percent of patients treated appear to have a sustained immune response after vaccination, which may reduce their risk of developing a more invasive cancer in the future. The results of the study were published online this month of Cancer and in the January issue of the Journal of Immunotherapy.

The researchers say the results provide new evidence that therapeutic breast cancer vaccines may be most effective for early, localized disease, and when the treatment attacks a protein critical to cancer cell survival.

“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!
Further information:
http://www.uphs.upenn.edu

More articles from Health and Medicine:

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>