A bold experimental treatment has finally succeeded in accomplishing a goal that has eluded doctors for decades: it has trained the immune systems of cancer patients to search out and kill cancer cells.
The New York Timesreports, in a novel twist, that the doctors used a disabled form of HIV-1, the virus that causes AIDS, to deliver the new genes that would program the person’s own cells to attack the cancer.
The University of Pennsylvania doctors have tried the experimental treatment in three leukemia patients, two of whom went into full remission and one of whom has had a partial remission in which his leukemia remains in lessened form.
They published the results of their experiment with the first patient, William Ludwig, in the New England Journal of Medicine and Science Translational Medicine.
Results in first patient
The doctors — Dr. Carl June of the Abramson Cancer Center at the University of Pennsylvaniaand colleagues Dr. David L. Porter, Bruce Levine and Michael Kalos — began by removing a billion of Ludwig’s T-cells, which are white blood cells that fight tumors and viruses.
They then altered the genes of the T-cells so they would attack cancer, and returned those modified T-cells to his bloodstream.
For the first ten days, nothing happened. But then, according to the Times, “hell broke loose in his hospital room. He began shaking with chills. His temperature shot up. His blood pressure shot down. He became so ill that doctors moved him into intensive care and warned that he might die. His family gathered at the hospital, fearing the worst.”
But within a few weeks, the fevers subsided, leaving no trace of cancer in their wake. No leukemic cells were found in his blood or bone marrow, and doctors calculated that two pounds of cancer cells had been killed off.
A year later, Ludwig’s remission remains complete. He has gained 40 pounds, plays golf, does yard work and travels with his wife in an R.V. Before the study, he sometimes could barely get out of bed and frequently suffered bouts of pneumonia. “I have my life back,” he told the Times.
How the therapy works and uses the HIV virus
In order for T-cells to kill cancer cells, they must be able to do several things: recognize the cancer, fight it, multiply and continue living inside the patient. Previous attempts to make T-cells do all these things failed, resulting in cells that, for instance, could only temporarily fight tumors.
However, this experiment enabled the modified T-cells to multiply to 1,000 to 10,000 times the amount originally altered by the researchers. In those numbers, they wiped out the cancer and then gradually diminished, but there remains a population of memory cells that could proliferate if needed.
The particular type of leukemia treated in this case was chronic lymphocytic leukemia, which afflicts B-cells. The doctors gave the T-cells genes that would make them find and attack a protein found on all B-cells, whether they are healthy or leukemic.
But it is not easy to decide which genes to insert and how to insert them. Viruses are natural delivery vehicles because they specialize in invading the genes of cells. In this case, because doctors wanted to modify T-cells, the AIDS virus was chosen because it naturally invades T-cells.
While other researchers have used HIV-1 to insert DNA into cells in gene therapy for other diseases, Dr. June and his colleagues were the first to use it in gene therapy for cancer patients.
This particular form of HIV-1 was no longer dangerous because other researchers had added DNA from humans, mice and cows and from a virus that infects woodchucks and another that infects cows.
But this type of therapy is not without risks. In other experiments, engineered T-cells have attacked the healthy tissue of patients. And, having been done in only three patients, the new T-cell treatment is not yet proven to work and has not yet been mass-produced by the drug industry.
Dr. June said his team’s next focus is using T-cells to attack solid tumors, such as mesothelioma and ovarian and pancreatic cancer.
Watch them discussing their method in this video:
via: The New York Times
photo: the engineered T-cells with magnetic beads attached to them; the beads are removed prior to infusion into the patient. (University of Pennsylvania)
