Researchers from The University of Texas M. D. Anderson Cancer Center are reporting the first study to show that vaccination with a peptide that is abnormally expressed on myeloid leukemia cells can produce a complete molecular remission in some patients.
The experimental vaccine produced an immune response in 60% of patients tested - or 20 of 33 evaluable patients, according to their study, which is being presented at the annual meeting of the American Society of Hematology.
Of those 20 patients who mounted an immune response against their cancer, 14 had an overall survival of four years, and none of the 13 patients who did not have such a response lived that long, they say. Three patients are in “molecular remission” in which there is no evidence of the disease remaining.
“These are very promising results in a group of patients who were quite sick, and who normally would live for just months,” says the study’s lead investigator, Jeffrey Molldrem, M.D., an associate professor in the Department of Blood & Marrow Transplantation.
“Not only can we say that some of these patients had an immune response, but they also went into remission, and that has never been demonstrated to occur after peptide vaccination before. And for patients who showed an immune response but did not go into remission, progression of their cancer was slowed down compared to patients who did not have an immune response to the vaccine,” he says. “Of course, we have much more research to do, especially in testing greater numbers of patients within each disease group.”
Nearly all of these patients had either active or relapsed acute myelogenous leukemia (AML) or refractory chronic myelogenous leukemia (CML) - forms of leukemia in which there is a dangerous accumulation of immature cells in the bone marrow - or they had high-risk myelodysplastic syndrome (MDS), a precancerous bone marrow disorder.
The vaccine is made from the PR1 peptide, a small part of a protein found on the inside of leukemia cells. Delivery of the vaccine induces immune cells that recognize the PR1 peptide, which are recruited to the bone marrow that contains leukemia,” says Molldrem. “The PR1 peptide is naturally present in normal bone marrow cells and since the target protein is overexpressed on leukemia cells, it directs immune T-cells to kill the leukemia and leave normal cells alone.”
Like many vaccines used to induce immunity against infections, this one appears to create an immune system “memory” for the PR1 peptide, conferring long-lasting protection. “Patients only get the vaccine three times, yet we have been able to measure an immune response in patients four years after treatment,” says Molldrem.
©2004 The University of Texas M. D. Anderson Cancer Center
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