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Earlier use of Prostate Cancer Vaccines urged by Hopkins Scientists

Somewhat dated, but interesting article.

Timing is everything when it comes to killing prostate cancer cells with specially tailored vaccines, say scientists testing the drugs in mice at the Johns Hopkins Kimmel Cancer Center.

"The window of opportunity is narrow for vaccination, designed to reinvigorate the immune system's attack on cancer cells, and it occurs right after hormonal therapy begins to wipe out the tumor and immune cells outnumber cancerous ones," according to Charles Drake, M.D., Ph.D., assistant professor of oncology and director of the research which is published in the March issue of Cancer Cell.

Charles Drake, M.D., Ph.D., assistant professor of oncology
In the Hopkins studies with mice bred to develop prostate cancer, Drake and his collaborators at the University of Connecticut found that the animal's immune system recognizes the cancer but fails to mount an attack, probably because immune cells become tolerant of the slow-growing cancer.

"The mice get used to the cancer very slowly over time," Drake says. "But we found that if we use the vaccine to activate the immune system right after we give the mice hormone therapy to shrink their tumors, T-cells start a reaction against the cancer."

T-cells are responsible for recognizing foreign cells and marking them for destruction. Changes in proteins on the T-cell's surface give clues to whether they "see" the cancer and are targeting it. Those cells that have been ignoring the cancer need time to regroup and multiply in order to mount an attack, the scientists say.

T-cells multiplied three times as much in prostate cancer mouse models that were given vaccinations immediately after hormone therapy as opposed to those not receiving hormone therapy. "It's not immunological magic," Drake notes. "It makes sense that when hormone therapy gets rid of cancer cells and the protein antigens they carry, it's easier to re-educate the immune system to fight cancer cells when they come back in smaller numbers."

"If our findings are confirmed, we believe human vaccines stand a better chance of getting T-cells to respond after most of the tumor is destroyed by hormone therapy," says Drake. "The strategy thereafter would be to continue activating the immune system with repeated vaccines and delay the time until the patient needs more hormone therapy, other treatments or lives old enough to die from other causes."

"Most prostate cancer vaccines currently are tested on men whose cancers are growing and no longer responsive to hormone therapy," says Drake. "Fewer than 20 percent of men respond to vaccines alone." Drugs that suppress male hormones such as testosterone, which fuels prostate cancer, are one of the main treatment alternatives for early relapse and helps stall cancer growth.

No clinical trials are yet available for the earlier vaccine regimen.

Prostate cancer is the leading cause of cancer deaths in American men. The average time to relapse after beginning hormone therapy is approximately two years.

http://www.hopkinsmedicine.org/Press_releases/2005/03_15a_05.html

also from the same researcher, another interesting article from last year

Immunotherapy: Making it Better

The idea of using a man’s own immune system to fight cancer has intrigued scientists for years. It makes perfect sense: The body is supposed to attack harmful invaders, and it does a great job protecting us from most of the germs, viruses, and disease-causing agents we encounter throughout our lives. It even fends off most cancer for decades.

But this idea, called cancer immunotherapy, has not progressed as successfully as scientists had hoped it would. One major hindrance may be a well-meaning but misguided group of cells called regulatory T cells,which shut off the body’s immune response.

Drake and colleagues, using a mouse model of prostate cancer, have been able to isolate regulatory T cells from prostate tumors. His next step will be to characterize these cells, “with the eventual goal of blocking their function so that immunotherapy for prostate cancer will be more successful.”

Earlier experiments have provided some clues about how these regulatory cells work, he adds. “They seem to depend on a substance known as transforming growth factorbeta (TGF-β).” Drake will determine whether blocking TGF-β will help immunotherapy for prostate cancer work more effectively. All of this work, in turn, “should provide new insights into the role of regulatory T cells in prostate cancer, and help us to design combination immunotherapy strategies that will be more successful in treating patients.”

http://urology.jhu.edu/newsletter/prostate_cancer87.php

Interestingly, John Hopkins is also home to Mario Eisenberger, a very skeptical reviewer of Provenge immunotherapy studies...who emphasizes that Provenge didn't delay disease progression while questioning whether it was taxotere or provenge that contributed to the increased survival observed in the trials...he also just happens to be lead investigator of the ATLAS study (Adjuvant Taxotere and Leuprolide Acetate Study)- involving more than 2,000 patients from more than 20 countries world-wide.

It will test whether immediate hormonal therapy using leuprolide acetate (which stops the production of testosterone) with or without taxotere, started right after surgery, works better than treatment with the same drugs given months or years later, when the cancer shows the first sign of recurrence (when the PSA starts climbing).

http://urology.jhu.edu/newsletter/prostate_cancer827.php