UCSF enrolling patients for trial testing immunotherapy treatment for cancer

By Leslie Harris

The UCSF Comprehensive Cancer Center is enrolling patients for three clinical
trials to investigate a new treatment for kidney cancer, prostate cancer and
melanoma. The trials aim is to determine if early immune cells, called stem
cells, can be collected and transferred from a patient’s sibling into the
patient to attack the cancer.

Using a similar treatment, investigators at the National Institutes of Health
(NIH) recently demonstrated that this technique could be used to fight advanced
kidney cancer. The tumors shrank in ten of the 19 patients in the NIH trial.
And three of those patients had complete responses, with all evidence of cancer
disappearing. The study was reported in the September issue of the New England
Journal of Medicine.

Mark Frohlich, MD, and Peter Sayre, MD, PhD, both UCSF assistant professors of
medicine, are co-investigators for the UCSF trials. They hope to confirm the
NIH results in kidney cancer and determine if these donated stem cells can also
be used to target prostate cancer and melanoma.

“The principle behind the study is to replace the patient’s immune system with
that of his or her sibling,” Frohlich said. “The hope is that the transplanted
immune system will be able to attack the cancer in a way that the patient’s own
immune cells have been unable to do.”
The donor’s immune system must be compatible, or “matched” with the patient’s.
There is approximately a 25 percent chance that siblings will have matched
immune systems, Frohlich said.

Stem cells are early blood cells that give rise to all the different blood cell
types, including cells responsible for mounting an immune response. The
transfer of another person’s stem cells is called an “allogeneic” stem cell

This technique has been used for decades to treat leukemia and other blood
cancers, but is just now being tested on solid cancers using a much less toxic
approach. With leukemia and other blood cancers, stem cell transplantation is
used to replenish the immune cells and other blood cells after patients are
given high doses of chemotherapy, often combined with total body irradiation.
This therapy works to kill the cancer residing in the bone marrow. As a
byproduct of this intensive treatment, the normal bone marrow is irreparably
damaged requiring that a new blood and immune system be infused into the
patient. The patient’s immune system is suppressed to enable the transferred
cells to grow and multiply, or “engraft.” The transferred stem cells repopulate
the bone marrow with new blood cells that create a new immune system. Research
has shown this new immune system often plays a key role in killing any residual
cancer left in the bone marrow after the chemotherapy.

But side effects of standard allogeneic transplants are significant. Patients
who undergo this procedure are typically hospitalized for weeks to months. Many
patients die from complications of the transplant procedure, Frohlich said.

Recent research suggests that stem cells can engraft with much less toxic
preparative regimens. In this newer approach, the goal is to allow the
transferred immune system to deliver the anti-cancer effect, rather than the
chemotherapy. In the UCSF trials, Frohlich and Sayre plan to deliver the
treatment on an outpatient basis. Patients will be hospitalized only if
complications arise.

Here’s how the UCSF treatment works: The donor is given injections of a growth
factor for five days to stimulate stem cells to spill out of the bone marrow
and into the blood stream. The donor is connected intravenously to a machine
that collects the blood cells and returns the remainder of the blood to the
donor. Prior to transfer of these cells to the patient by infusion, the patient
is treated with a low dose of total body irradiation and special medications to
prevent his or her immune system from rejecting the transferred cells. The
immunosuppressive medications are slowly tapered off over several months, and
the patient’s blood is tested periodically to determine if the donated cells
have engrafted. Some patients will receive additional donor cells that have
been frozen and stored if they need them.

There are still significant risks to these “low dose” stem cell transplants,
Frohlich said. “While the hope is that the transferred cells will attack the
cancer, they may also attack a patient’s normal cells,” he said. This
condition, called “graft versus host disease” may cause skin rashes, fever, low
blood counts and liver damage. In addition, suppressing the patient’s immune
system while waiting for the donated cells to engraft places the patient at
risk of infection, and possibly cancer acceleration.  In the NIH study, two of
the 19 patients died of treatment related complications and it took
approximately four months on average for patients to respond to the treatment.

Frohlich and Sayre plan to enroll five to 10 patients in each of the trials. If
they can demonstrate the treatment is safe and shows some evidence of tumor
shrinkage—or in the case of prostate cancer, lower levels of a protein in the
blood that indicates cancer—they will expand the trials to include additional

The prostate cancer trial is being funded by CaP Cure, an organization that
provides funding for prostate cancer research. For more information on the
kidney and prostate cancer studies, please call (415) 885-7331. For the
melanoma trial, please call 885-7546.