Moores UCSD Cancer Center Treats 
1st Patient on Phase II Gene-Therapy Trial

Researchers at the Rebecca and John Moores UCSD Cancer Center, in conjunction with Tragen Pharmaceuticals, today launched a Phase II gene-therapy clinical trial for patients with chronic lymphocytic leukemia (CLL), an incurable condition afflicting more than 50,000 people in the United States. 

The first patient on the study, Carol Scelsi of Chula Vista, received an infusion this morning of her own leukemia cells that had been genetically modified to induce her immune system to mount a cancer-killing response. Scelsi will remain hospitalized for 24 to 48 hours for observation.

This study is based upon promising results from an earlier study conducted at UCSD in which 11 patients were each treated with a single injection of their own modified leukemia cells. In that Phase I study, the researchers removed leukemia cells from the patient’s blood, manipulated the cells to render them harmless, and then genetically modified them to induce the patient’s own immune system to launch a powerful, killing response. The immune response prompted by the modified cells destroyed not only the harmless modified cells, but also active leukemia cells. 

All but one of those patients had a significant drop in the number of leukemia cells found in their blood, and a reduction in the size of their lymph nodes.

“That was the first time we had seen a response that dramatic in the history of treating this disease,” said Thomas Kipps, M.D., Ph.D., who was the principal investigator for the Phase I study.

The Phase II study is designed to determine if multiple injections will maintain the leukemia cell counts at low levels for a longer period, according to the Cancer Center’s M. Wayne Saville, M.D., principal investigator for the Phase II study and associate professor of clinical medicine at UCSD School of Medicine.

“If this therapy can keep the cancer cells in check with no side effects, or with tolerable side effects for the patient, we may be able to turn CLL from a killer into a manageable, chronic disease much like diabetes,” said Saville.

Investigators will administer the modified cells, known as ISF 154 (Tragen), as a mono-therapy to 40 patients in two treatment cohorts. In the first cohort, 20 patients who have failed chemotherapy will receive up to 10 doses of ISF 154 over a 20-week period. In the second cohort, 20 patients with advanced disease who have declined chemotherapy will receive up to 10 doses of ISF 154 as front-line therapy.

“The Phase II clinical trial will evaluate the efficacy of ISF 154 as a mono-therapy to eliminate leukemic cells in the blood and lymph nodes, while rebuilding the patient’s natural immune system,” said Charles Prussak, Ph.D., president and CEO of Tragen Pharmaceuticals.

The Phase II clinical trial is also offered through researchers affiliated with Dana-Farber/Partners CancerCare, a collaboration of Dana-Farber Cancer Institute, Brigham and Women's Hospital and Massachusetts General Hospital in Boston.

Science Behind the Treatment

The concept for this approach was born in the UCSD laboratory of Thomas Kipps, M.D., Ph.D., an internationally known cancer immunologist. There he combined healthy, active T cells with leukemic B cells. Normally T cells kill abnormal cells, but in this case there was no reaction.

Kipps and his colleagues then discovered that a signal delivered through a surface molecule known as CD40 was deficient in CLL. Moreover, they found that stimulation of CD40 on these leukemic cells turned them into “flashing neon signs” for the attention of T cells and other components of the immune system.  The researchers then introduced genes into the leukemia cells that directed the cells to produce a protein capable of stimulating CD40, called CD40-ligand. They found that the genetically modified leukemia cells made CD40-ligand and could stimulate not only themselves, but also the CD40 on non-modified bystander leukemia cells. This resulted in a powerful response against the leukemia by the patient’s own immune system. This laboratory research and the promising results of the Phase I clinical trial led to the formation of Tragen Pharmaceuticals, a San Diego-based biopharmaceuticals company, and its first product, ISF 154.

Rebecca & John Moores UCSD Cancer Center National Cancer Institute CLL UCSD School of Medicine

Background on CLL

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. CLL is the most common adult leukemia.

Founded in 1979, UCSD Cancer Center was recently renamed the Rebecca and John Moores UCSD Cancer Center in honor of the Moores leadership gift to the Center. The Center is one of just 40 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. 

Tragen Pharmaceuticals is a biopharmaceutical company focused on activating the power of the immune system to combat certain cancers. Its novel therapeutic platform of stabilized TNF-based compounds is designed to activate dormant B-cells and rally T-cells to selectively attack blood- and tissue-based cancers. The company’s first drug candidate is ISF 154 for the treatment of chronic lymphocytic leukemia (CLL).