Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hybrid vaccine demonstrates potential to prevent breast cancer recurrence

18.05.2012
Novel adjuvant therapy shows promise for women with a history of breast cancer in Phase II clinical trial

A breast cancer vaccine already shown to elicit a powerful immune response in women with varying levels of HER2 expression has the ability to improve recurrence rates and is well tolerated in an adjuvant setting, according to new research from a clinical trial led by researchers at The University of Texas MD Anderson Cancer Center.

The findings, released today, will be presented on Monday, June 4 in an oral presentation at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO). It builds on previous research showing the vaccine, known as AE37, to safely and effectively raise immunity against human epidermal growth factor receptor 2 (HER2) – an oncoprotein that promotes tumor growth and is expressed to some extent in 75-80% of breast cancer tumors.

The researchers found that patients who received the vaccination had an estimated recurrence rate of 10.3% compared to 18% in the control group at a median follow up of 22 months. This represented a 43% reduction in the risk of recurrence.

"The vaccine educates the immune system to recognize HER2 as an invader," said Elizabeth Mittendorf, M.D., assistant professor in the Department of Surgical Oncology at MD Anderson and the trial's national principal investigator. "By introducing it into women who have had breast cancer, our goal is to instruct the immune system to immediately recognize any recurring cancer cells and orchestrate an attack."

Building a Powerful Vaccine

The AE37 peptide vaccine used in this study is a hybrid modified to increase its potency in generating an immune response specific to cancer cells expressing HER2. It consists of a fragment of the HER2 protein (AE36), a MHC Class II epitope, linked to an Ii-Key peptide. Together, they work to stimulate a robust CD4+ T cell response, prompting the components of the immune system to seek and destroy tumor cells.

To help T cells better recognize AE37, researchers also paired the vaccine with an immune stimulant known as granulocyte/macrophage colony stimulating factor (GM-CSF). The vaccine is injected under the skin similar to a tetanus shot. The initial series consists of inoculations given monthly for six months followed by four cycles of boosters every six months.

Preventing Breast Cancer Relapse

Most experimental drugs are first evaluated in patients with metastatic disease, when tumors have undergone drastic changes, including immunoescape – a mechanism that allows tumor cells to evade elimination by the immune system. "There's very little chance a single peptide vaccine like AE37 will overcome a tumor at this stage of disease," said Mittendorf. "For this reason, it's more realistic to use the vaccine to prevent recurrence rather than to treat a large mass of already present cancer cells."

In the Phase II randomized clinical trial of 201 disease-free breast cancer patients, 103 women received the AE37 peptide plus GM-CSF adjuvantly; a control group of 98 patients received GM-CSF alone. All patients had varying levels of HER2 expression.

Results showed that the vaccine was well tolerated in the patients and toxicity was minimal; short-term side effects included redness at the injection site, flu like symptoms and bone pain. In addition to being consistent with earlier data which showed a significant immune response to the vaccine, the study also revealed how the vaccine affects recurrence rates.

The vaccine appears to prevent recurrence and work in women with any level of HER2 expression. Further, the findings draw parallels to other vaccines we now have advanced to later phase trials, Mittendorf said. MD Anderson currently has three different types of HER2-based peptide vaccines in various stages of testing and development. AE37 is the only one that targets CD4+ T cells.

"Off the Shelf" Capability

Among the benefits of a peptide-based vaccine are that it's simple to produce and administer, and that it can be easily exported to the community compared to other available vaccines. Mittendorf noted whereas dendritic cell vaccines require patients to go to the hospital for a large blood draw that is shipped to a processing center – a complicated and expensive process – peptide vaccines can be administered to patients "off the shelf."

The vaccine possibly offers advantages to today's adjuvant therapies as well. "Adjuvant therapies currently used for breast cancer are taken ongoing. Otherwise, their effect to block cancer development is diminished," said Mittendorf. "In theory, once a response is generated with immunotherapy, we can expect a longer lasting therapeutic effect without repeated dosing.

"This is an exciting time for immunotherapy as we transfer knowledge from the lab to clinic. There's a renewed enthusiasm to manipulate the immune system therapeutically – from vaccines and antibodies to combining these modalities and improving response rates."

The findings will be presented at ASCO by Timothy J. Vreeland, M.D., resident at Brooke Army Medical Center. The trial is funded in part by Antigen Express, the company that licenses the vaccine technology. Based on this study, Antigen Express plans to apply for a special protocol assessment from the US Food and Drug Administration to continue Phase III research needed on the vaccine.

Other researchers contributing to the study include: Diane Hale, M.D., Alan Sears, M.D. G. Travis Clifton, M.D., Nathan Shumway, D.O. and George Peoples, M.D., from Brooke Army Medical Center; Sathibalan Ponniah, Ph.D., from Uniformed Services University of the Health Sciences; and Sonia Perez, Ph.D., Michael Papamichail, M.D., Ph.D. and Alexandros Ardavanis, M.D. from Saint Savas Cancer Hospital, Cancer Immunology and Immunotherapy Center in, Athens, Greece.

Laura Sussman | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Health and Medicine:

nachricht Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern

nachricht Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

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: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>