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 One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

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: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>