Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pancreatic tumors are marked for immunotherapy

01.12.2009
Pancreatic tumors can be identified by a readily detectable marker that shows promise as a basis for immune therapy against the disease, according to research at Washington University School of Medicine in St. Louis.

The marker is mesothelin, a protein normally found on mesothelial cells that line the body cavities. Several types of cancer cells make large amounts of mesothelin, which then circulates in the blood.

Mesothelin levels in the blood were shown in earlier studies to predict survival in patients with ovarian cancer and mesothelioma (a cancer of mesothelial cells). The researchers wanted to know if elevated blood levels of mesothelin could be used as a biological indicator for pancreatic disease. The study, published this month in Clinical Cancer Research, also examined whether the protein could be useful for immune-based cancer treatments.

"All pancreatic tumor specimens we tested displayed mesothelin on them, and the protein could be detected in the blood of 99 percent of our study patients with pancreatic cancer," says co-senior author Peter Goedegebuure, Ph.D., research associate professor of surgery. "Other studies suggest that mesothelin plays an essential role in the development and growth of cancer, making it an ideal target for therapy."

Pancreatic adenocarcinoma, the most common type of pancreatic cancer, strikes about 40,000 Americans per year. However, it is often not diagnosed until advanced stages of the disease because symptoms are non-specific or completely absent. Fewer than five percent of patients will survive more than five years after diagnosis.

"If we can turn on the immune system to attack cells that have mesothelin, that might become an important part of pancreatic cancer therapy," says co-senior author William G. Hawkins, M.D., a pancreatic cancer surgeon with the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University. "Because mesothelin aids tumor growth, loss of mesothelin could make cancer cells behave more like normal cells. That means even if immunotherapy only knocked out the mesothelin in pancreatic cancer cells instead of killing the cells, it could still be effective. That's what's so exciting about mesothelin as a therapeutic target."

The study showed that mesothelin in the blood was significantly higher in 73 of 74 patients with pancreatic adenocarcinoma when compared to healthy people. There was no relationship between stage of disease or tumor volume and level of circulating mesothelin. Additionally, five patients with benign pancreatic disease who were tested had high levels of circulating mesothelin.

"A number of benign or inflammatory conditions of the pancreas increase mesothelin levels as much as pancreatic cancers do," says Hawkins, who is also associate professor of surgery at Washington University School of Medicine. "So our study suggests that blood mesothelin levels will not be useful for diagnosing pancreatic cancer or predicting patient outcome."

However, the researchers discovered that immune cells taken from pancreatic cancer patients could be coaxed to target mesothelin.

"Mesothelin-specific immune cells are present in pancreatic cancer patients and can be activated," Goedegebuure says. "And those results suggest that we could potentially design a vaccine to boost the immune response to mesothelin to target pancreatic cancer cells."

Before that becomes a reality, the team will need to overcome obstacles that have previously limited the success of immune-based strategies targeted at cancer, says Hawkins.

"We need three things to come together," Hawkins says. "We need to identify the correct antigens, and this paper suggests mesothelin is one. We need to introduce the antigen in a way that looks dangerous to the human body to elicit an immune response. And we need to interfere with the ability of cancers to turn down the immune response near them."

Researchers have made progress on these fronts. Hawkins is conducting a clinical trial with pancreatic cancer patients of an agent that may boost activation of tumor-specific immune cells. Other researchers at Washington University are testing vaccines that train the immune system to recognize cancer-specific antigens and methods of reducing cancer's ability to suppress immune responses.

"The real breakthroughs in cancer immunotherapy are going to come when we bring these kinds of independent projects together into combined therapies," Hawkins says.

Johnston FMc, Tan MCB, Tan BR, Porembka MR, Brunt EM, Linehan DC, Simon PO. Plambeck-Suess S, Eberlein TJ, Hellstrom KE, Hellstrom I, Hawkins WG, Goedegebuure P. Circulating mesothelin protein and cellular antimesothelin immunity in patients with pancreatic cancer. Clinical Cancer Research Nov. 1, 2009; 15(21):6511-6518.

Funding from the National Institutes of Health, the American Association of Cancer Research/PanCAN and the Barnes-Jewish Hospital Foundation supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Siteman Cancer Center is the only federally designated Comprehensive Cancer Center within a 240-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine. Siteman has satellite locations in West County and St. Peters, in addition to its full-service facility at Washington University Medical Center on South Kingshighway.

Gwen Ericson | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

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: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

Im Focus: Scientists improve forecast of increasing hazard on Ecuadorian volcano

Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).

The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New thruster design increases efficiency for future spaceflight

16.08.2017 | Physics and Astronomy

Transporting spin: A graphene and boron nitride heterostructure creates large spin signals

16.08.2017 | Materials Sciences

A new method for the 3-D printing of living tissues

16.08.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>