Source: DGNews  |  Posted 2 years ago

ST. LOUIS, Mo -- December 1, 2009 -- Pancreatic tumours can be identified by a
readily detectable marker, mesothelin, that shows promise as a basis for immune
therapy against the disease, according to a study conducted at the Washington
University School of Medicine and published in the November 1 issue of
Clinical Cancer Research.

Mesothelin is a protein expressed on mesothelial cells lining the body
cavities. Several types of cancer cells produce 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. The researchers
wanted to know if elevated blood levels of mesothelin could be used as a
biological indicator for pancreatic disease. The study also examined whether
the protein could be useful for immune-based cancer treatments.

“All pancreatic tumour specimens we tested displayed mesothelin on them, and
the protein could be detected in the blood of 99% of our study patients with
pancreatic cancer,” says co-senior author Peter Goedegebuure, PhD, Washington
University School of Medicine. “Other studies suggest that mesothelin plays an
essential role in the development and growth of cancer, making it an ideal
target for therapy.”

“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, MD, Siteman Cancer Center at Barnes-Jewish Hospital
and Washington University, both in St. Louis, Missouri. “Because mesothelin
aids tumour 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 blood levels were significantly higher in 73
of 74 patients with pancreatic adenocarcinoma compared with healthy people.
There was no relationship between stage of disease or tumour volume and level
of circulating mesothelin. Additionally, 5 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 Dr. Hawkins. “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,” Dr. 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 Dr. Hawkins.

“We need 3 things to come together,” Dr. 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. Dr. Hawkins is conducting a
clinical trial with pancreatic cancer patients of an agent that may boost
activation of tumour-specific immune cells. Other researchers at Washington
University are testing vaccines that train the immune system to recognise
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,” Dr.
Hawkins says.

SOURCE: Clinical Cancer Research