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 Nanoparticles as a Solution against Antibiotic Resistance?
15.12.2017 | Friedrich-Schiller-Universität Jena

nachricht Plasmonic biosensors enable development of new easy-to-use health tests
14.12.2017 | Aalto 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: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>