June 27, 2003

Novel Immune Therapy for Leukemia
Tested at Moores UCSD Cancer Center

Researchers at the Rebecca and John Moores UCSD Cancer Center, in conjunction with Xcyte Therapies, Inc., of Seattle, are conducting a clinical trial of an experimental therapy for chronic lymphocytic leukemia (CLL) in which the patient's own T lymphocytes, a type of immune system cell, are modified to enhance their ability to mount a cancer-killing response.

Thomas Kipps, M.D., Ph.D. with patient, Mary Louise Armsby of Orinda, Ca. She is first patient to receive the experimental therapy, on June 2, 2003.

The first person to be treated, a 61-year-old woman from Orinda, CA., received an infusion of her modified T cells on June 2 and is doing well, according to the trial's principal investigator, Thomas Kipps, M.D., Ph.D.

"She tolerated the treatment well with no apparent major toxicities, so we're very pleased about that," said Kipps, an internationally known cancer immunologist. "This is the first time this approach has been used for CLL."

This clinical trial is offered only at the Moores UCSD Cancer Center, he said.

CLL is an incurable condition afflicting more than 50,000 adults in the United States, with 10,000 to 12,000 new cases diagnosed each year. Current treatments are unsatisfactory because responses do not last and the treatments can produce many side effects. One of the most serious is an immune deficiency that develops because the cancer-killing drugs also kill T cells, the cells that naturally help to fight infection and cancer.

Kipps and his Cancer Center colleagues hope that, if successful in clinical trials, this cellular immune therapy might provide an effective new treatment for this disease. In addition, this approach also might help overcome problems with the more standard types of treatment.

"Standard treatment generally is toxic to the T cells and results in immune deficiency, which can lead to serious illness and even death in some patients with this disease," said Kipps. "If we harvest the T cells prior to such therapy, activate them while the patient receives therapy, and then re-infuse the activated T cells after therapy, we hope to see a T cell anti-leukemia effect and restore immune function at the same time. It's sort of like having your cake and eating it too."

In this study, participants undergo a process called leukapheresis, which removes a small amount of the patient's blood, separates the T cells and returns the remaining blood to the patient. The T cells are sent to Xcyte, Inc., where they are cultured with beads coated with two antibodies that are specific for the cell-surface molecules CD3 and CD28. This process increases the number of T cells and activates them to enhance their ability to generate an immune response. The modified T cells are then infused back into the patient in the General Clinical Research Center at UCSD Medical Center, Hillcrest. The patient remains in this specialized research facility overnight and is monitored for any side effects to the cellular immune therapy, which may produce flu-like symptoms.

"The flu-like symptoms may occur when large numbers of leukemia cells are destroyed and their contents are released into the bloodstream," said Kipps.

This is a Phase I/II clinical trial, which means it is designed to determine safety and effectiveness. Participants will be followed closely for four months for any side effects, to evaluate their response over time to the modified T-cell product, and to gauge the anti-leukemia effect of the treatment.

The Rebecca and John Moores UCSD Cancer Center is one of just 39 centers in the United States to hold a National Cancer Institute (NCI) designation as a Comprehensive Cancer Center. As such, it ranks among the top centers in the nation conducting basic and clinical cancer research, providing advanced patient care and serving the community through outreach and education programs.

For further information about the study, call the study's research nurse at 858-822-2405.

I.D. Information

Thomas Kipps, M.D., Ph.D., is professor of medicine and chief of the Division of Hematology/Oncology in the UCSD School of Medicine. He is also deputy director for research at the Moores UCSD Cancer Center, director of the national CLL Research Consortium, and associate director of the UCSD Gene Therapy Program.

Background on CLL

CLL is the most common adult leukemia, and is currently incurable. On average, patients survive six to seven years.

CLL is a chronic disease in which B-lymphocytes, immune cells in the body, accumulate because they do not undergo apoptosis -- programmed cell death. The increase in abnormally functioning B-lymphocytes is associated with a number of clinical features, including an enlarged liver, spleen and lymph nodes, and abnormalities in the immune system. B-cells normally make proteins such as antibodies. In patients with CLL there is a defect in the function of the normal immune system, which renders the patient susceptible to infections and other immune system-related disorders.

Currently, the cause of CLL is unknown. Many cases are detected by routine blood tests in people with no symptoms. An increased incidence of CLL has been noted in people with certain autoimmune diseases. The incidence increases with age, to 15 people out of 100,000 by 70 years of age.

News Media Contact:
Nancy Stringer

UCSD Health Sciences Communications HealthBeat: http://health.ucsd.edu/news/