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Trials Begin For General
Cancer Vaccine
By Joe Grossman - UPI Science News
http://www.vny.com/cf/News/upidetail.cfm?QID=153945
1-22-01



There is a saying in the world of cancer researchers: Don't mention"cancer" and "cure" in the same sentence. Perhaps that truism should benoted here.
 
Nevertheless, cancer researchers in Boston have begun the first trials ofa general purpose cancer vaccine, a treatment designed to stimulate the bodyto subdue most types of cancer with its own immunity defenses. The vaccinerelies on the fact that roughly 85 percent of all human cancer cells expressan enzyme called telomerase that normal cells do not. While researchers have conducted more than one hundred trials ofcancer-specific vaccines -- with some notable though preliminary successes-- a general cancer vaccine has never been attempted in humans.
 
The researchers, working at the Dana Farber Cancer Institute in Boston,will attach part of an enzyme found in most cancers to cells from apatient's own immune system. The resulting complex will be injected into thepatient, where the group hopes it will prod immunity components called Tlymphocytes to seek out and destroy cancer cells.
 
Lead researcher Dr. Bob Vonderheide is careful not to overstate hisexpectations, however. "At this point it's an interesting idea that we want to test. There's noguarantee," Vonderheide, also on the faculty of Harvard Medical School, toldUnited Pres International. "The number one question for this upcoming trialis: Will we be able to get over the threshold necessary to achieve aclinical response in a safe way?"
 
Dr. Jeffrey Schlom, a cancer vaccine researcher at the National CancerInstitute, Bethesda, Md., explained the fundamental difference in a vaccineapproach to cancer treatment. In chemotherapy, he said, "it's like putting a nerve gas over abattlefield. It's just going to go everywhere and all those people who arenot wearing gas masks are going to die. And if you are wearing a gas maskyou're resistant and you'll go on to fight.
 
"When you're dealing with immunology you're giving these dendritic cells,"which activate the T cells against the tumor, he continued. "You're dealingmore like hand-to-hand combat in a battle. So if you have evenly matched oroverwhelming force you can overcome the tumor. If you have a thousand(times) more tumor cells than your T cells you're not going to do very well.So it may be a numbers game."
 
Vonderheide's phase I trial will treat up to 18 patients whose cancershave metastasized, or spread -- those with stage IV breast or prostatecancer, leukemia or lymphoma -- and who have exhausted other therapyoptions. Like all phase I clinical trials, the team will emphasize testingthe vaccine's safety and leave true efficacy studies to phase II and IIItrials later.
 
The investigators will take blood from a patient, then isolate, mix andultimately attach the dendritic cells to a part of the telomerase enzymecalled the telomerase catalytic subunit, or hTERT.
 
The researchers are crafting a custom vaccine for each patient. The process is costly and takes about a week. The dendritic cell-hTERT complexwill then be injected under the skin of the volunteer patients every otherweek for a month and a half. The researchers hope that the speciallystimulated T lymphocytes will seek out and destroy telomerase-rich cancercells.
 
Telomerase protects the ends of chromosomes from the inevitable frayingthat occurs when a growing cell splits into two daughters. Its lack innormal adult cells contain imposes a natural lifespan. But if by mistake acell manufactures much of the enzyme, that cell can become what researcherscall immortal -- cancerous -- and divide indefinitely. While Vonderheide's approach is logical, other researchers in the fieldare even more cautious in their hope for a cure.
 
Dr. Elie Gilboa of Duke University's Center for Genetic and CellularTherapies told UPI, "By itself, telomerase (subunit attached to dendriticcells) would not be fully or sufficiently effective." Gilboa, who did the first animal research with the technique, found a"significant" response by tumors to a telomerase-dendritic cell experimentin mice. However, he does not believe the response was enough to eventuallyjustify an approved vaccine unless further strides are made in thetechnique.
 
For example, the numbers game described by Schlom could tip in favor ofthe vaccine if, as Gilboa noted, researchers can grow both dendritic cellsand T lymphocytes outside the body, and in greater numbers. Vonderheide expects to grow large numbers of cells in a subsequentexperiment.
 
Durham, N.C.-based Gilboa did say there's no question that if thetechnique works, large factories would be built to make the custom vaccines.The road from clinical trial to market -- if indeed the vaccine makes itthat far -- is probably at least seven years away. NCI's Schlom himself is concerned about possibly triggering a reaction tothe body's own telomerase-containing stem cells, he said.
 
However, the approach "is just so new and so different that one just hasto do it and see," he told UPI. "I don't know of any so-called universalcancer antigen, other than perhaps telomerase."
 
The Damon Runyon-Walter Winchell Foundation and the CaP Cure Foundationare funding the three-year, $2,000,000 experiment.
 
c. 2001 by United Press International. All rights reserved
 
 
 
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