"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.
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.
The research was conducted with collaborators at the University of Connecticut Health Center. Participants include Adam J. Adler, Amy D.H. Doody, Marianne A. Mihalyo, Ching-Tai Huang, Erin Kelleher, Sowmya Ravi, Edward I. Hipkiss, Dallas B. Flies, Eugene P. Kennedy, Meixiao Long, Patrick W. McGary, Lee Coryell, William G. Nelson, and Drew M. Pardoll.
Photo of Charles Drake, M.D. available upon request.
On the Web: www.hopkinskimmelcancercenter.org