Researchers have come up with a method for destroying cancer cells using death cap mushroom (Amanita phalloides) toxin, without harming the body. The death cap mushroom, which resembles the common white button mushroom, contains one of the most deadly poisons found in nature, a-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 way to annihilate 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 tumour growth. Two injections of higher doses of the antibody even caused complete tumour 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 tumour 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 tumours originate from such epithelial tissues. Many of these, such as pancreatic cancer, breast and ovarian cancers, bile duct carcinomas and tumours 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 tumour 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,” Moldenhauer added.