Treating Bowel Cancer with Gene Therapy: Too Much of a Good Thing

A major problem associated with most drugs used to cure cancer is that they are not specific for the malignant cells. Drug doses sufficient to get rid of the cancer can therefore produce serious or fatal damage to the patient as a whole. Our immune system is a much more specific tool and investigators have therefore tried to use it to more selectively attack tumors. Until recently, this attack has used semi-synthetic proteins called monoclonal antibodies. Now, however, it is possible to use the actual cells of the immune system to directly attack cancers, particularly of the skin (melanoma) and blood (lymphoma and leukemia).

In Molecular Therapy, Dr. Steven Rosenberg's group extends this cellular approach to bowel cancer. They report good news and bad news. The good news is that a component of the immune system called T lymphocytes can be engineered to recognize a structure called carcinoembryonic antigen (CEA) that is present at high levels on bowel cancer cells. In three patients receiving their own engineered T lymphocytes, the investigators found they could shrink the tumor. The bad news is that the engineered T lymphocytes were so efficient at recognizing CEA that they could see it even in the much smaller amounts present on normal gut cells. So they attacked those normal cells as well, causing severe bowel inflammation.

Investigators hope they will be able to "dial down" the sensitivity to CEA so that only when the target is present at high levels (i.e. on cancer cells) will the T lymphocytes be stimulated to attack. In that way we will have an effective immune therapy for bowel cancer that can truly distinguish friend from foe.