This was the heading in a recent article in The New York Times, a year ago a leukemia patient was the first person to be treated in a new experiment at the University of Pennsylvania.
Doctors removed a billion of his T-cells — a type of white blood cell that fights viruses and tumors — and gave them new genes that would program the cells to attack his cancer. Then, the altered cells were dripped back into his veins
At first, nothing happened. But after 10 days, 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.
A few weeks later, the fevers were gone. And so was the leukemia. There was no trace of it anywhere.
A year later, he is still in complete remission.
His doctors have not claimed that he is cured — it is too soon to tell — nor have they declared victory over leukemia on the basis of this experiment, which involved only three patients. The research, they say, has far to go; the treatment is still experimental, not available outside of studies.
But scientists say the treatment that helped him, described recently in The New England Journal of Medicine and Science Translational Medicine, may signify a turning point in the long struggle to develop effective gene therapies against cancer. And not just for leukemia patients: Other cancers may also be vulnerable to this novel approach — which employs a disabled form of HIV-1, the virus that causes AIDS, to carry cancer-fighting genes into the patients’ T-cells.
In essence, the team is using gene therapy to train a person’s own immune system to kill cancer cells.
Two other patients have undergone the experimental treatment. One had a partial remission, the other had a complete remission. All three had had advanced chronic lymphocytic leukemia and had run out of chemotherapy options.
Dr. Carl June, who led the research and directs translational medicine in the Abramson Cancer Center at the University of Pennsylvania, said that the results stunned even him and his colleagues, Dr. David L. Porter, Dr. Bruce Levine and Dr. Michael Kalos.
Other experts in the field said the results were a major advance.
To make T-cells search out and destroy cancer, researchers must equip them to do several tasks: recognize the cancer, attack it, and multiply and persist inside the patient. A number of research groups have been trying to do this, but the T-cells they engineered could not accomplish all the tasks.
The University of Pennsylvania team seems to have hit all the targets at once. Inside the patients, the T-cells modified by the researchers multiplied to 1,000 to 10,000 times the number infused, wiped out the cancer and then gradually diminished, leaving a population of “memory” cells that can quickly proliferate again if needed.
The researchers say they are not sure which parts of their strategy made it work — special cell-culturing techniques, the use of HIV-1 to carry new genes into the T-cells, or the particular pieces of DNA that they selected to reprogram the T-cells.
Chronic lymphocytic leukemia, is a cancer of B-cells, the part of the immune system that normally produces antibodies to fight infection. All B-cells, whether healthy or leukemic, have on their surfaces a protein called CD19. To treat patients with the disease, the researchers hoped to reprogram their T-cells to find CD19 and attack B-cells carrying it.
To modify their patients’ T-cells, June and his colleagues used a disabled form of HIV-1. They are the first ever to use HIV-1 as the vector in gene therapy for cancer patients (the virus has been used in other diseases).The virus is a natural for this kind of treatment, June said, because it evolved to invade T-cells.
“It incorporates the ability of HIV to infect cells but not to reproduce itself,” he said.
To administer the treatment, the researchers collected as many of the patients’ T-cells as they could, by passing their blood through a machine that removed the cells and returned the other blood components. The T-cells were exposed to the vector, which transformed them genetically, and then were frozen. Meanwhile, the patients were given chemotherapy to deplete any remaining T-cells, because the native T-cells might impede the growth of the altered ones. Finally, the T-cells were infused back into the patients.
While promising, the new techniques developed by the University of Pennsylvania researchers are not without danger to patients. Engineered T-cells have attacked healthy tissue in patients at other centers. Such a reaction killed a 39-year-old woman with advanced colon cancer in a study at the National Cancer Institute, researchers there reported last year in the journal Molecular Therapy.
June said his team hopes to use T-cells against solid tumors, including some that are very hard to treat, like mesothelioma and ovarian and pancreatic cancer. But possible adverse reactions are a real concern, he said, noting that one of the protein targets on the tumor cells is also found on membranes that line the chest and abdomen. T-cell attacks could cause serious inflammation in those membranes and mimic lupus, a serious autoimmune disease.
Even if the T-cells do not hit innocent targets, there are still risks. Proteins they release could cause a “cytokine storm,” high fevers, swelling, inflammation and dangerously low blood pressure — which can be fatal. Or, if the treatment rapidly kills billions of cancer cells, the debris can damage the kidney and cause other problems.
Even if the new T-cell treatment proves to work, the drug industry will be needed to mass produce it. But June said the research is being done only at universities, not at drug companies.For the drug industry to take interest, he said, there will have to be overwhelming proof that the treatment is far better than existing ones.
Before the study, the patient , Ludwig was weak, suffered repeated bouts with pneumonia and was wasting away. Now, he is full of energy. He has gained 40 pounds.
His wife something he considered profound. “She said, “We don’t know how long it’s going to last. Enjoy every day,”’
“That’s what we’ve done ever since.”
And so say all of us ……
