Turning T-cells into cancer-fighting guided missiles
Could this be the precursor to a melanoma vaccine?
Last Updated September 4, 2006
Mark Origer, 53, of Watertown, Wis., feared he wouldn't make the wedding of his daughter Katie last fall. But after undergoing an experimental gene therapy treatment for what he was told was end-stage melanoma, he is now, almost two years later, disease free. (Origer family/Associated Press)
A team of scientists led by Dr. Steven Rosenberg at the National Cancer Institute in the United States developed a gene therapy method that seems to cause melanoma to regress, and they have two survivors of the lethal skin cancer to prove it.
According to the president of the Canadian Institutes of Health Research, Dr. Alan Bernstein, this is considered an "important advancement" in cancer treatment because it's effectively using "our body's own mechanisms, whether immunological, hormonal or biological, as attack weapons against cancer."
"It's an important proof of principle," said Bernstein. "It actually worked in two patients. The question is, can you actually extend that to other patients and other cancers?"
Rosenberg and his team are seen as pioneers using the body's own T-cells to identify malignant tumors. Once modified, these fighters can stay in the bloodstream long enough to obliterate the cancerous cells. Some optimistic scientists even say that these engineered T-cells could be the forerunner to a type of cancer vaccine.
By genetically modifying white blood cells (T-cells) extracted from melanoma victims, the researchers were able to save the lives of two men taking part in the NCI's early stage clinical trial, launched in December 2004.
The two were part of a group of 17 terminally ill patients who were undergoing Rosenberg's experimental gene therapy treatment for advanced melanoma. They all had a life expectancy of less than six months. Fifteen of the patients succumbed to their illness, but the two patients who are still alive 18 months after the treatment are the source of hope for the medical community.
Cancer biologist and director of the Research Institute at Toronto's Mount Sinai Hospital, Dr. Jim Woodgett, told CBC Online, "This is significant. It wasn't a fluke, it worked in two patients, not one."
Woodgett said Rosenberg and his team have succeeded in "bolstering our T-cells by infusing the correct specificity, the right trigger, to recognize and shoot melanoma cells."
The method: using the body's immune system to attack tumors
Rosenberg and his colleagues use a method they call adoptive cell transfer.
How they do it
- Normal lymphocytes are removed from a patient in the advanced phases of melanoma. Lymphocytes are made up of white blood cells, B-cells and T-cells. The lymphocytes are obtained by taking a blood sample from the patient.
- The part of the immune cell endowed with the best components for fighting cancerous tumors is isolated.
- These cells are infused with a retrovirus that transports specific genes or T-cell receptors (TCRs) encoded to identify and attach themselves to molecules (called antigens) on the tumour cells.
- These genetically modified super TCRs are multiplied in the lab.
- The patient's supply of regular lymphocytes is depleted before the patient is injected with the engineered super immune TCRs and the patient is given an immune system strengthening treatment called Interleukin 2. The TCRs then activate the lymphocytes to destroy the cancer cells.
The results achieved by the Rosenberg' team have been 30 years in the making.
The project's measured success is seen as a boon for gene therapy, which is at times regarded with suspicion because of failed experiments that have resulted in fatalities.
No toxic side effects were reported in any of the patients who took part in the trial.
A second chance at life
Mark Origer of Watertown, Wis., is one of the two patients who have benefited from Rosenberg's gene therapy.
The team at the NCI are scheduled to meet with the 53-year-old every three months for the next five years to monitor his progress. The precaution is necessary because the scientists can't guarantee that the cancer won't reappear.
The other beneficiary was a 39-year-old man.
Possible reasons why the other 15 patients didn't respond to the treatment
- Patient's body inactivated the T-cells.
- The melanoma became resistant to those T-cells.
- Incorrect dose applied.
- Stronger receptors required.
"All 17 patients were terminal," said Woodgett. "The survival of the two patients is directly linked to this procedure, which is experimental."
The future of gene therapy for cancer patients
Currently, the "highly experimental" treatment can only be used for melanoma patients who already have the kind of lymphocytes that recognize tumours as abnormal cells.
But the potential of this type of methodology is far reaching. According to Woodgett, "It can be applied to other cancers and theoretically to any infectious disease."
Rosenberg's team plans to expand its clinical trials to include gene therapy for breast and colon cancer.
What's interesting is that it's an "individual treatment using a natural mechanism," Bernstein said. "But, it's too early to say it will be a widely applicable method. We're not there yet."
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