Investigational approach uses patient's own tumor cells to harness immune system
As part of a national multi-center study, researchers at the University of Maryland Greenebaum Cancer Center in Baltimore are testing a custom-made vaccine for low-grade non-Hodgkin's lymphoma that uses each patient's own tumor cells to combat the cancer.
"This type of low-grade follicular lymphoma has traditionally been highly treatable, but essentially incurable," says Aaron P. Rapoport, M.D., the director of lymphoma-gene medicine at the Greenebaum Cancer Center and the chief investigator for the study. "This technique for harnessing the immune system may result in long-term disease remission and potential cures for some patients."
So far, four people have been enrolled in the study at the Greenebaum Cancer Center, but researchers hope to recruit a total of 12 to 15 patients in the Phase III clinical trial. The first patient to be vaccinated, a 45-year-old Baltimore woman, started her treatment earlier this month after completing a course of chemotherapy.
About 480 patients are expected to participate in the nationwide study at 25 institutions in the United States and Canada. The study is sponsored by Genitope Corporation, a California-based biotechnology company developing new therapies for treating cancer.
To be eligible for the study, patients must have been diagnosed with follicular lymphoma, a common form of cancer of the lymphatic system, and have not yet received treatment. If enrolled, they will have a small biopsy taken of their cancer, either from a lymph node or bone marrow, which will be sent to Genitope Corporation to make a vaccine unique to each patient.
The customized vaccine is designed to target a tumor-specific marker, or idiotype, which, like a fingerprint, is unique to every lymphoma patient. Once injected, the vaccine is intended to activate the immune system to attack cells that have the idiotype protein on their surface, namely the cancer cells.
"Without this, the body's immune system is somewhat blind to the lymphoma. Lymphomas and other types of cancers use mechanisms to evade the body's immune system," says Dr. Rapoport, an associate professor of medicine at the University of Maryland School of Medicine.
He said that in earlier clinical trials, about two-thirds of the patients showed positive immunological responses to the vaccinations. "But it is difficult to know the clinical impact of that," he says. "Does it mean that they have better responses or longer-lasting responses? That's what this study is designed to show."
In this trial, patients first receive eight rounds of chemotherapy with three drugs - cytoxan, vincristine and prednisone. If they experience at least a 50 percent remission, they remain in the study and are observed for another five months while their bodies rest from the chemotherapy.
If there is still no progression of their disease, two-thirds of the patients receive a vaccine crafted from their own tumor cells, plus an immune system stimulant, while one-third receive a vaccine using only a carrier protein and the stimulant, which may also activate the immune system in a beneficial way.
With the selections made at random by computer, neither the doctors nor the patients know which type of injections the patients will receive.
The patients will receive a series of seven vaccinations over six months and then have follow-up scans to check on the progress of their disease for the next two years. The results of the clinical trial are expected within two to three years, depending on when the last patient is treated.
Non-Hodgkin's lymphoma is the fifth most common cancer in the United States, with about 57,000 new cases diagnosed each year. Low-grade follicular lymphomas are generally treated with radiation if they are localized or chemotherapy if they are widespread, Dr. Rapoport says. The cancer responds well to treatment, but is likely to recur.
"I believe this technology offers the potential for better treatment results than we have previously seen," Dr. Rapoport says.