CONTACT: BECKY SOGLIN
Iowa City IA 52242
(319) 335-6660; fax (319) 384-4638
Release: Aug. 27, 2001
UI team begins study of vaccine to treat prostate cancer
IOWA CITY, Iowa -- A team of University of Iowa Health Care physicians and
researchers has launched the nation's first clinical trial of an adenovirusprostate-specific
antigen (PSA) vaccine for treatment of prostate cancer that has failed other
The Phase I study is designed initially to test the optimal dosage at which
the vaccine, a type of gene therapy, can safely be given to patients.
The clinical study is being co-led by David Lubaroff, Ph.D., UI professor
of urology and microbiology, and Richard Williams, M.D., the Rubin H. Flocks
Chair in Urology, and professor and head of the department. The vaccine was
designed in Lubaroff's laboratory and also draws on UI research led by Timothy
Ratliff, Ph.D., the Anderson-Hebbeln Professor of Urology.
The UI Health Care trial also will help determine how well the vaccine stimulates
an immune response and if this response has a therapeutic effect on prostate
Eligible patients will specifically be selected by the investigators through
a screening process and will include men whose prostates have been removed
or have been treated by radiation. In addition, the eligible study participants
are already receiving hormone treatment and have a tumor in the prostate or
cancer that is known to have metastasized from the prostate (spread to other
parts of the body such as the bone).
Some of the patients will previously have been treated at the Holden Comprehensive
Cancer Center at the UI. Patients will be selected to receive different dosages
of vaccine in one of two types of injectable forms, either a saline-based
solution or a gel matrix.
"This is the first study in a series of four vaccines we're developing
that may help us treat patients with hormone-resistant prostate cancer,"
Williams said. "Our hope is that this vaccine or one of the other three
vaccines, or perhaps two or more of them in combination, will be effective
in halting the progression of prostate cancer."
Lubaroff said that vaccine therapy for any cancer is a relatively new area
of research. In addition to the UI study, investigations on other prostate
cancer vaccines are under way at other institutions.
"The advantage of a vaccine is that it can use the patient's own immune
system to treat the cancer rather than administering other drugs that may
or may not be specific to the cancer," Lubaroff said. "In addition,
the vaccine can help enhance the immune response over time."
Two patients already have received the treatment, which involves an injection
and an overnight stay at the UI Clinical Research Center, Williams said.
"The immunization is similar to the one a person gets for diphtheria-pertussis-tetanus,
in that it's injected just barely under the skin," Williams said.
To create the vaccine, the team used a virus that causes the common cold
but which has been engineered to be non-infective in humans. The disabled
virus, known as an adenovirus, can then be used as a vector, or carrier, of
other genes that researchers insert into the virus.
"We inserted the gene for prostate-specific antigen into the disabled
virus," Lubaroff explained. "Through an injection, the virus enters
cells and helps produce PSA. The hope then is the body will respond to the
presence of PSA with an immune response that fights the cancer."
Specifically, the PSA introduced via the vaccine should stimulate the immune
system to produce anti-PSA antibodies and lymphocytes, which lead to the destruction
of PSA-producing cells. This is expected to help shrink tumors.
"Because the patients in this trial will have measurable disease, we
should be able to see if their lesions have decreased in size within a few
weeks after the immunization treatment," Williams said. "We also
can monitor the prostate-specific antigen, which is a measure of the volume
of cancer in a patient. The PSA levels should decrease if the tumor actually
responds to the therapy."
Because the patients in the study have a minimally functioning or no prostate,
any PSA present will be known to be produced by tumor cells. Eighteen patients
will be treated in the Phase I study. Williams said that if the initial investigation
is successful, it will be expanded to include more patients.
The researchers will also try to determine whether a special gel, a collagen
matrix known as Gelfoam, helps the vaccine maximize its potential.
In pre-clinical studies done in collaboration with Ratliff's laboratory
and based on research by Robert Siemens, M.D., former UI research fellow in
urology, Lubaroff's laboratory showed that the gel helps the virus reach its
destination and induce a stronger anti-PSA response.
"Our laboratory findings indicate the Gelfoam augments the potential
of the PSA-containing virus we inject," Lubaroff said. "This augmentation
may be due to a slower, more sustained release of the virus in the body or
by the activation of other biologically active cells."
Lubaroff, an immunologist, added, "This is an exciting and unique opportunity
to see if we can use a person's own body to fight cancer through a vaccine."
Other UI investigators involved in the study include Jack Gerstbrein, a
physician assistant in urology; Brian Link, M.D., assistant professor of internal
medicine; and Michael O'Donnell, M.D., associate professor of urology. Additional
UI individuals participating in the study include nurses in the Holden Comprehensive
Cancer Center and the Clinical Research Center.
Prostate cancer is the second leading cause of death among men in the United
States. African American males are at a higher risk for the disease than are
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