Biological ‘Smart Bomb’ Destroys Cancers : Medicine: Scientists report that an engineered antibody finds and kills human tumors that had been implanted in rats.
A biological “smart bomb” can find and kill cancer cells and has cured laboratory animals infected with human cancers, researchers said in a study published Friday.
The study, appearing in the journal Science, said the core of the so-called “smart bomb” is a laboratory-engineered antibody that naturally finds and attaches itself to human cancer cells.
Pamela A. Trail, a scientist at the Bristol-Myers Squibb Pharmaceutical Research Center in Princeton, N.J., said the antibody has been chemically linked to an anti-cancer drug called doxorubicin. The antibody and the drug combine to make what is called an immunoconjugate that the researchers have named BR96-DOX.
Trail said that in laboratory experiments, BR96-DOX has been able to achieve cancer cures in a high percentage of mice and rats that had been implanted with human lung, colon and breast cancer.
When BR96-DOX is injected, it circulates in the blood until it finds and links up with an antigen found most frequently on the surface of human cancer cells. Trail said the BR96-DOX is taken into a cell, where the smart bomb goes off.
“It is the doxorubicin which is released inside the cell that actually kills the cell,” she said.
Dr. Louis M. Weiner, a researcher at the Fox Chase Cancer Center in Philadelphia, said there has been other research using antibody cancer therapy, but that “very few have been associated with as convincing pre-clinical evidence of anti-tumor activity.”
He said it was “particularly impressive” that the animals used in Trail’s study bore tumors that had spread and, thus, more closely mimicked cancer in humans.
Dr. Mark Ratain, an oncologist at the University of Chicago, said the fact that the researchers reported such a high rate of cure among the test animals is “very exciting.”
Trail said the study found that although BR96-DOX did attack some normal tissue, the test animals could easily tolerate high doses of the drug.
“The damage that may have been done to normal tissues was entirely reversible,” she said.
In their experiments, the researchers implanted cells from the human cancers into laboratory mice and rats. The research animals had been bred to have no immune system reaction to the human cells. As a result, the transplanted human tumors grew rapidly in the rodents.
“We gave the animal a tumor of a reasonable size,” Trail said. “You could see it, you could feel it.”
Some of the animals were designated as experimental controls. They were divided into groups that received either no treatment, injections of a conventional cancer drug or injections of an antibody that did not carry a cancer drug.
The rest of the test animals received BR96-DOX in various doses.
“The untreated animals grew very large tumors,” Trail said. There was some tumor growth delay in the other two groups of control animals, but cancers did not recede or go away.
In the animals receiving high doses of BR96-DOX, however, there were actual cancer cures, she said.
“What we call a cure is when the tumor completely regresses and you can’t feel the tumor,” said Trail. “We call it a cure if (the tumor) didn’t reappear for up to a year.”
BR96-DOX seemed to have the same effect on each of the human cancers tested, but the most detailed evaluation was done for human lung cancer tumors, she said.
Some doses of BR96-DOX cured 70% of the mice with extensive invasion from transplanted human lung cells. In rats, Trail said, there were lung cancer cure rates of up to 94% at some doses.
The researcher said she expects her laboratory to apply to the Food and Drug Administration in about six months for a license to conduct experimental human trials with BR96-DOX. She declined to estimate how long it might take to complete human tests of the drug.
Eight other Bristol-Myers Squibb researchers were co-authors of the report in Science, the journal of the American Assn. for the Advancement of Science.
