LEUKEMIA drug shows early promise, stokes hope for `magic bullet' against cancer

Wednesday, July 25th 2001, 12:00 am
By: News On 6

BOSTON (AP) _ A genetically engineered drug shows great early promise in tracking down and killing a rare leukemia, raising doctors' hopes in the long quest for a magic bullet against cancer.

Eleven of the 16 patients treated in a study of the drug were left with no readily detectable trace of the disease.

The experimental drug relies on a piece of antibody from a mouse's immune system to latch tightly onto the cancer cells, while shunning normal cells. A bacterial poison fused to the antibody is then carried inside the cancer cells and kills them.

Doctors have long tested mouse antibodies as drugs. Researchers said this drug _ and similar ones under study _ may eventually prove useful for some other types of cancer, too.

``People thought this kind of thing was going to happen 25 years ago, and it just didn't happen,'' said immunologist Dr. Terry Strom of Beth Israel Deaconess Hospital in Boston. ``Something's happening now.''

He co-wrote an accompanying editorial on the leukemia study, which was published Thursday in The New England Journal of Medicine.

The researchers at the National Cancer Institute in Bethesda, Md., developed and tested the drug, a so-called immunotoxin known as BL22, on 16 patients with hairy cell leukemia untreatable by the usual chemotherapy.

The blood and bone marrow cancer, named for the hairy look of the cells under a microscope, accounts for about 2 percent of all leukemia cases. Many hairy cell cases are easily controlled, but the disease can sometimes be fatal.

The early experiment was designed largely to find out if the drug can be taken safely. The researchers said three patients were clearly given too little or were immune to the bacterial toxin.

Of the 13 others, 11 were left completely free of the disease, judged by standard techniques, after an initial cycle of treatment. During two years of follow-up, only three of those 11 needed more treatment.

``We expected that some patients would respond to the treatment,'' said senior investigator Dr. Ira Pastan. ``But we didn't imagine in our wildest dreams that almost all of the patients would go into complete remission.''

Two patients did develop serious blood clotting in their kidneys, but the researchers said they learned it can be avoided simply by giving enough fluids.

Mouse antibodies were studied for potential as human drugs because it was impossible to make human antibodies until more recently. In this study, the patients' immune systems did not appear to reject the mouse antibody as foreign, in part because just a small segment was used.

The attached toxin came from a Pseudomonas bacterium. As an unwanted invader, it can spur pneumonia or other potentially fatal infections in patients with weakened immune systems. In the drug, it does not sicken patients because it is carried right into cancer cells.

Lead author Dr. Robert Kreitman said that if larger tests succeed, the drug may eventually become a first-line treatment, instead of a last resort, for some patients.