‘Breakthrough’ method rids patients of advanced cancer
August 10, 2011
In what is being hailed as a potential cancer breakthrough, three men suffering late-stage leukemia have been cured using their own, genetically reprogrammed immune systems.
The technique transforms blood-borne T-cells into “serial killers” that hunt down and obliterate cancer cells, leaving healthy tissue unharmed, according to a pair of studies published simultaneously in two prominent journals.
“I’m getting goosebumps,” says University of Pennsylvania pathologist Michael Kalos, lead author of one of the studies.
“The promise of this is profound. If this repeats in more patients . . . it shows that we can, with amazing effectiveness, blow away cancer cells,” Kalos said in an interview.
Two studies describing the process were released Wednesday by the New England Journal of Medicine and Science Translational Medicine.
“For the field of immune therapy it’s a really exciting advance,” says Pamela Ohashi, head of immune therapy at the Ontario Cancer Institute.
“It actually provides a new way to manipulate the immune system,” Ohashi says.
Although it takes in only three patients, Ohashi says the results presented were so robust they should send excitement throughout her field.
Kalos explains that the technique works much like a vaccine, training the immune system to target cancer cells, just as inoculations coax it to fight off viruses.
To do this, researchers isolated immunological T-cells from the blood of the three leukemia patients and genetically reprogrammed them using a virus vector that inserted a new gene into their DNA.
This gene coaxed the T-cells to create an antibody — known as chimeric antigen receptor or CAR — that would specifically target structures on the surface of cancer cells.
The newly armed T-cells were then injected back into the respective patients where they sought out and bound themselves to the cancer cells and killed them.
More importantly, however, the reprogrammed hunters caused other T-cells to multiply each time they attacked, creating more killers with each slain cancer cell.
“Within three weeks the tumours had been blown away, in a way that was much more violent than we ever expected,” Dr. Carl June, a senior study author, said in a statement.
“In addition to an extensive capacity for self-replication the infused T-cells are serial killers. On average each infused T-cell led to the killing of thousands of tumour cells,” said June, a University of Pennsylvania pathologist.
It’s estimated the scant number of T-cells originally injected into the patients killed more than two pounds of tumour cells in each of the men, whose blood and bone marrow were replete with cancer.
After a year, microscopic analysis of their blood could find no trace of cancerous cells, Kalos says.
“I am still trying to grasp the enormity of what I am part of and of what the results will mean to countless others with (leukemia) or other forms of cancer,” one of the patients, none of whom were named, said in a written statement.
Kalos says it appears that, like a vaccine, the T-cells also left the patients with a lingering protection, which would reactivate the immunological attack if cancer returned.
“If leukemia does come back, those T-cells (appear to be) armed and ready to eliminate it,” he said.
Each of the men had been suffering from chronic lymphocytic leukemia, a slow-acting form of the blood ailment that can linger for years before radical therapies like marrow transplants become necessary.
But Kalos says there is no reason to think the killer T-cell therapy would not work on more lethal “hard tumour” cancers like breast, prostate or lung.
He says each type of cancer cell has unique surface structures that T-cells could be similarly reprogrammed to hone in on.
“You can target prostate cancer, for example, by targeting any of the surface molecules that have been shown to be present on prostate cancer,” Kalos says.
Researchers have attempted to use modified T-cells to fight cancer in several previous trials, but always with lacklustre results.
Kalos says he does not know why his team’s attempt appears to have worked, but he suspects the unique lentivirus used to insert the modifying genes played a role.
“This seems to be a novel approach to harnessing the power of the patient’s own immune system to battle Chronic Lymphocytic Leukemia (CLL) and perhaps other related leukemias,” says Dr Michael Wosnick, head of research with the Canadian Cancer Society.
“Although the initial study was limited to 3 patients, this may pave the way for better treatments of these diseases, and that is of course what we all want to see,” he said via email.
The researchers could only treat three patients because they ran out of the virus, which was derived from HIV.
Kalos says the team has managed to acquire more of the virus — which cost $250,000 for the first three treatments — and will begin new trials in the coming months.