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STUDY SUGGESTS DEATH CAP MUSHROOM POISON ARRESTS PANCREATIC CANCER IN MICE

ScienceDaily.com, April 2, 2012

The mere thought of an identification error

sends a chill down the spine of any mushroom

lover. The death cap mushroom (Amanita phalloides),

which resembles the common white

button mushroom, contains one of the most

deadly poisons found in nature, α-amanitin.

This substance kills any cell without exception,

whether it be healthy or cancerous. At the

German Cancer Research Center (Deutsches

Krebsforschungszentrum,

DKFZ) and the National Center for

Tumor Diseases Heidelberg, immunologist Dr. Gerhard Moldenhauer,

jointly with biochemist Professor Dr. Heinz Faulstich,

Max Planck Institute for Medical Research, has now developed a

method for destroying cancer cells using the dreaded fungal toxin

without harming the body.

The trick to accomplish this is to deliver the poison directly to the

right address in the body using something that virtually serves as

a cab. In this case, the cab is an antibody whose highly specific

arms attach to a cancer-typical cellular surface protein called

EpCAM. The fungal toxin is linked to the antibody in a stable

chemical conjugation.

In the culture dish, the poison-loaded antibody arrested the growth

of pancreatic, colorectal, breast, and bile duct cancer cell lines.

In mice bearing transplanted human pancreatic cancer, a single

antibody injection was sufficient to inhibit tumor growth. Two

injections of higher doses of the antibody even caused complete

tumor regression in 90 percent of the animals. Even the higher

doses did not cause any poison-related damage to the liver or other

organs of the animals.

EpCAM, the protein chosen by the Heidelberg immunologists as

the tumor cell recognition structure, is a characteristic membrane

protein of epithelial cells. This type of cells lines all inner and

outer surfaces of the body. Most malignant tumors originate from

such epithelial tissues. Many of these, such as pancreatic cancer,

breast and ovarian cancers, bile duct carcinomas, and tumors

of the head and neck, produce too much EpCAM—and this is

frequently associated with an extremely poor prognosis of the

disease. EpCAM is therefore considered a suitable target structure

for attacking tumor cells.

“Treatments with unconjugated antibodies against EpCAM have

already been tested in clinical trials such as for breast cancer. They

were intended to attack the cancer solely with the weapons of the

immune system, but they turned out to be clinically ineffective,”

said Gerhard Moldenhauer. “However, our amanitin-conjugated

antibody has a much greater potential for killing cancer cells.”

Each antibody is linked to between four and eight toxin molecules.

Amanitin is regarded as very suitable for this purpose. It is small

enough not to be recognized as foreign by immune cells, while

it is also robust enough to lend itself to chemical conjugation.

“When developing toxin-conjugated antibodies you have to take

an awful lot of things into account,” Moldenhauer explains. “The

cancer cell has to regularly take the target molecule including

the attached antibody into its interior, for this is the only place

where the poison can act. In the cell’s interior, the poison needs

to detach from the antibody or else it will not be effective. At the

same time it is absolutely vital that it does not get lost while it is

being carried through the body, because this could cause severe

adverse side effects.”

The dosage of the amanitin antibody needs to be determined with

the utmost care. One problem is that liver cells are extremely

sensitive to the fungal toxin; another is that other healthy cells

carry the EpCAM molecule as well and are therefore endangered.

However, the results obtained in mice give reason to be optimistic,

according to Gerhard Moldenhauer: “Even at high doses we have

not detected any organ damage in the animals. We therefore expect

that there is a sufficient therapeutic window for a dosage that kills

cancer cells while leaving healthy tissue unaffected.”

Moldenhauer, who has many years of experience in developing

therapeutic antibodies, already has plans for amanitin-conjugated

guided missiles against other cancers. In particular, certain types

of leukemia and lymphoma cells also carry highly specific surface

molecules which lend themselves as target structures for poison loaded

antibodies.

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AL2O3

that was great info man..interesting they using a common mushroom.... that is awesome if it works in humans. the mushroom might even become rare then.

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