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Gene Therapy
Treatment for Canine Cancer
By Karen Earles
Brandy, a 12-year-old yellow Labrador retriever, has been
through a lot in the last two years of her life. In 1996 Brandy's
owners, Richard and Eileen Salcedo of Castle Rock, Colorado,
noticed the dog was limping; trying to keep her weight off
her right rear leg. An examination led Brandy's veterinarian
to suspect cancer. The dog was then taken to the Veterinary
Referral Center (VRC) of Colorado. The Center is a collection
of veterinarian specialists, including a neurologist, a cardiologist,
three orthopedic surgeons, a dermatologist and an oncologist.
By night, the Center serves as an emergency veterinary hospital.
Brandy was diagnosed with osteosarcoma -- bone cancer. The
100 pound retriever's right rear leg was amputated and she
was given chemotherapy treatments for about six weeks.
According
to Robyn Elmslie, DVM, veterinary oncologist at the Center,
amputation followed by chemotherapy is the standard treatment
for bone cancer in dogs. This treatment however, will not
cure the dog's cancer. The average survival time after treatment
is about one year. Dogs with osteosarcoma will usually die
because the cancer has spread to the lungs. After this happens,
the average survival time is about two months. After chemotherapy,
x-rays of Brandy's chest showed that the cancer had spread
to her lungs.
For the
past six years Elmslie and her husband Steven Dow, DVM, Ph.D.,
an immunologist at the National Jewish Medical Research Center
in Denver, had been evaluating gene therapy for the treatment
of cancer. The gene interleuken 2 showed promising results.
"Interleuken 2 is a normal gene found in all species," says
Elmslie. "It plays a role in regulating the immune response.
What we want to do is develop a stronger immune response.
It's the immune system that does the tumor killing, not the
actual product that we are providing. We're giving the tool
that will hopefully help the body's immune system do its work."
This form
of immunotherapy involves combining interleuken 2 with a fatty
acid called a lipid. It is given intravenously to dogs diagnosed
with osteosarcoma. The gene combined with the lipid is able
to target the lung tissues. "In earlier pre-clinical studies
with mice, we have observed a marked immune stimulation after
intravenous administration of lipid-DNA complexes, both systematically
and in the lungs," says Dow.
The intravenous
therapy has had a significant effect on Brandy. After 12 weeks,
the tumors in her lungs were notably smaller than they had
been six weeks earlier. Brandy has been receiving gene therapy
for more than a year, and the lung tumors are extremely small.
Losing a leg does not seem to bother the big retriever, although
she does have difficulty climbing stairs, say her owners.
Brandy spends most of her time trying to get some sleep despite
the antics of the Salcedo's other two dogs, Amanda a two-year-old
Maltese, and Maggie, a four-year-old Basset hound.
A Little Help From Friends
The Morris
Animal Foundation lists cancer as the number one cause
of disease related-deaths among cats and dogs. The Foundation
has sponsored 31 studies addressing different cancers. Cancer
studies received top priority when the Foundation's Scientific
Advisory Board met in June of this year to determine which
research projects would receive funding from the 50-year-old
foundation. When deciding which studies will be funded, the
three main criteria the advisory board looks for are scientific
soundness, relevancy (will it really help animals?) and humaneness
of procedure. This year the MAF is granting $1.6 million for
approximately 80 animal health studies.
Elmslie's
and Dow's study, "Intravenous Gene Therapy for Canine Pulmonary
Metastatic Cancer," is currently being funded by a foundation
grant and covers the study for osteosarcoma only. The Veterinary
Referral Center is involved with similar studies involving
other forms of cancer, such as melanoma, which are being funded
by other organizations.
The first
patient admitted into the study since the Foundation grant
was Yogi, an eight-year-old male Rottweiler. Like Brandy,
one of Yogi's rear legs was amputated and he received chemotherapy.
In order to be eligible for the study, a dog with osteosarcoma
must have the primary tumor removed and undergo chemotherapy.
"Yogi has been receiving the gene therapy treatments since
June and is doing very well," says Elmslie.
Will It Hurt?
"Any immune
stimulation is going to result in what we call flu-like symptoms,"
says Elmslie. "The reason people with colds or flu have these
symptoms is because their immune systems are being stimulated
by the virus. The symptoms we generally see in the dogs being
treated with the gene therapy are fevers. These usually occur
after the first few treatments and are typically resolved
with aspirin. Other potential side effects include listlessness
and loss of appetite, although we haven't seen very much of
that. Most pet owners have told us that by the time we get
to the fourth week of treatment, their pet's energy levels
have improved above what they were before therapy."
The Center
charges a $350 entry fee for each client which covers the
cost of the initial consultation and diagnostic tests. The
Foundation covers all fees for the 18-week osteosarcoma study
period. Committed to making sure that these animals are not
dropped from proper care after the allotted time, the Center
will cover any future treatments for the animals if the tumors
have responded to treatment. Because Brandy began her therapy
before the Foundation grant, the Center has absorbed the cost
of her treatment. Brandy still receives treatments about every
two months. It is unknown at this time how long she will have
to stay with the therapy, says Elmslie.
Paradigm Shift
When Mark
Morris, Sr., DVM, founded the Morris Animal Foundation in
1948, the main health concern for cats and dogs in the United
States was getting hit by cars. Pets usually did not live
long enough to suffer the illnesses of old age that plague
them today, says Rob Hilsenroth, DVM, executive director of
the Foundation.
"Back
then...we knew a lot about cattle, hogs and poultry because
the diseases they got affected us economically. But dogs and
cats weren't yet considered family members."
Pet owners
in those days probably would have thought twice about extended
medical therapy for their pets. "Richard has had Brandy since
she was a puppy, and she had never been sick before," says
Eileen Salcedo. "As long as she's able to have a good quality
of life, we feel we should try to give her that, just as we
would if she were one of our kids."
Elmslie
feels there is an increase in pet owners willing to go to
extremes such as amputation and chemotherapy to save the lives
of their companion animals. "I think it's sort of a philosophy,"
says Elmslie. "The popular term would be 'paradigm shift'.
People use the phrase 'prolong one's life,' but the issue
is not so much prolonging life as it is the pursuit of quality
of life. That's what we try to do at the Center. Whether it
be treatment for heart disease, kidney disease or cancer,
if the end result is a better quality of life then it is a
reasonable treatment. If the end result would be a poor quality
of life, then treatment would not be appropriate. I think
that's the philosophy that permeates our use of treatment
and I think that that's what most pet owners want."
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