DENVER, April 21 -- Reprogrammed immune cells could become targeted "killing machines" against prostate cancer, a researcher said here.
In the early stages of a phase I study, these reprogrammed T cells sharply reduced the levels of prostate specific antigen (PSA) in two patients with metastatic prostate cancer, according to Richard Junghans, M.D., Ph.D., of the Roger Williams Medical Center in Providence, R.I.
Within a few weeks of the infusion of the engineered cells, one patient's PSA level had fallen by half and the other's by 75%, Dr. Junghans reported at the annual meeting of the American Association for Cancer Research.
T cells, Dr. Junghans told reporters, are the "perfect killing machines" when faced with a cell infected with a virus. "We have to fool the T cells into thinking that the cancer has a virus infection," he said.
To do that, he and colleagues isolate a patient's T cells from a blood sample and use genetic engineering techniques to make them sensitive to a molecule that only occurs in prostate cancer -- prostate specific membrane antigen, or PSMA.
Over a period of weeks, the modified cells are amplified in culture. Meanwhile the patient undergoes chemotherapy to knock down his remaining lymphocytes, creating "hematopoietic space" for the engineered T cells.
Finally, he said, the cells are infused into the patient and begin attacking cells that express PSMA. A marker for that activity, Dr. Junghans said, is the level of prostate specific antigen.
The falling levels of PSA in the two patients treated so far were obtained despite the low dose of cells they were given -- about a billion each.
The researchers plan to test that dose in one more patient and then escalate the dose -- first to 10 billion in six patients and then to 100 billion in another six.
In the two patients treated so far, the falling PSA levels appeared to have bottomed without reaching zero -- possibly because the methods used to activate them caused them to enter a resting state without completely eradicating the cancer cells, Dr. Junghans said.
With the higher doses, he said, he hopes to see PSA levels fall all the way to zero.
"We are very hopeful that when we get to higher doses," he said, "all those activated (cells) may get us to 100% suppression before they go to the resting state."
Dr. Junghans said the redirected T cells are a "brave new world" for cancer treatment. "I predict the FDA will have approved one of these designer T-cell constructs -- if not this one, then another one -- as standard therapy in the next five or so years," he said.
Dr. Junghans' approach is a new twist on ideas that have been around for "two decades or more," said Louis Weiner, M.D., of Washington's Lombardi Cancer Center, who was not part of the research.
"What Dr. Junghans and colleagues have done is to really combine two critical elements" -- redirecting the T cells and creating space for them by chemotherapy, Dr. Weiner said.
He said while the idea is intriguing and the early results promising, "at the end of the day, we will need properly conducted efficacy trials."
But "the early returns are sufficiently encouraging that I certainly hope they continue doing the work," he said.
In the early stages of a phase I study, these reprogrammed T cells sharply reduced the levels of prostate specific antigen (PSA) in two patients with metastatic prostate cancer, according to Richard Junghans, M.D., Ph.D., of the Roger Williams Medical Center in Providence, R.I.
Within a few weeks of the infusion of the engineered cells, one patient's PSA level had fallen by half and the other's by 75%, Dr. Junghans reported at the annual meeting of the American Association for Cancer Research.
T cells, Dr. Junghans told reporters, are the "perfect killing machines" when faced with a cell infected with a virus. "We have to fool the T cells into thinking that the cancer has a virus infection," he said.
To do that, he and colleagues isolate a patient's T cells from a blood sample and use genetic engineering techniques to make them sensitive to a molecule that only occurs in prostate cancer -- prostate specific membrane antigen, or PSMA.
Over a period of weeks, the modified cells are amplified in culture. Meanwhile the patient undergoes chemotherapy to knock down his remaining lymphocytes, creating "hematopoietic space" for the engineered T cells.
Finally, he said, the cells are infused into the patient and begin attacking cells that express PSMA. A marker for that activity, Dr. Junghans said, is the level of prostate specific antigen.
The falling levels of PSA in the two patients treated so far were obtained despite the low dose of cells they were given -- about a billion each.
The researchers plan to test that dose in one more patient and then escalate the dose -- first to 10 billion in six patients and then to 100 billion in another six.
In the two patients treated so far, the falling PSA levels appeared to have bottomed without reaching zero -- possibly because the methods used to activate them caused them to enter a resting state without completely eradicating the cancer cells, Dr. Junghans said.
With the higher doses, he said, he hopes to see PSA levels fall all the way to zero.
"We are very hopeful that when we get to higher doses," he said, "all those activated (cells) may get us to 100% suppression before they go to the resting state."
Dr. Junghans said the redirected T cells are a "brave new world" for cancer treatment. "I predict the FDA will have approved one of these designer T-cell constructs -- if not this one, then another one -- as standard therapy in the next five or so years," he said.
Dr. Junghans' approach is a new twist on ideas that have been around for "two decades or more," said Louis Weiner, M.D., of Washington's Lombardi Cancer Center, who was not part of the research.
"What Dr. Junghans and colleagues have done is to really combine two critical elements" -- redirecting the T cells and creating space for them by chemotherapy, Dr. Weiner said.
He said while the idea is intriguing and the early results promising, "at the end of the day, we will need properly conducted efficacy trials."
But "the early returns are sufficiently encouraging that I certainly hope they continue doing the work," he said.
Note: This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Dr. Junghans did not report support or conflicts.
By Michael Smith, North American Correspondent, MedPage Today
Published: April 21, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Primary source: American Association for Cancer Research
Source reference: Junghans RP, et al "Phase I trial of anti-PSMA designer T cells in prostate cancer" AACR 2009; Abstract 5662.
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