Timing is everything when it comes to killing prostate
cancer cells with specially tailored vaccines, say
scientists testing the drugs in mice at the
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," said Charles Drake, assistant professor of
oncology and director of the research that is published in
the March issue of Cancer Cell.
In the Johns 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
"The mice get used to the cancer very slowly over
time," Drake said. "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 said.
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 said. "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," Drake said. "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," Drake said. "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 help stall cancer growth.
No clinical trials are yet available for the earlier
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 conduced 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