Home » Leading research in T cell therapies for lymphoma
Spring 2010 – Cancer Connection, The Methodist Hospital
Two clinical studies led by The Methodist Hospital’s Dr. Catherine Bollard have shown encouraging results in early stages as researchers use T cell therapy to attack the tumors of lymphoma patients. Bollard, a hematologist in the Center for Cell and Gene Therapy (CAGT), is the principal investigator in the studies involving lymphoma patients whose tumors are positive for the Epstein Barr virus (EBV). The virus has been found in the cancer cells of approximately 40 percent of lymphoma patients, suggesting that it may have a role in causing the disease.
In the studies—being conducted at Methodist, Texas Children’s Hospital and Baylor College of Medicine—researchers take blood from patients and train their T cells to attack the EBV proteins LMP1 and LMP2, which are expressed by the tumor cells. The studies use cytotoxic T lymphocytes (CTLs) specific for LMP1 and LMP2 (LMP-CTL). These tumor-killing cells are given as two infusions, two weeks apart in an outpatient setting.
One study using LMP-specific cells began in 2004 with patients receiving T cells that recognized the LMP2 protein on the lymphoma cells. In 2007, researchers began making the T cells specific to both LMP12 and LMP2. This study is sponsored by the National Institutes of Health (NIH). Bollard says it has been more effective to target both cells, since the tumor has “less chance of becoming clever and developing defenses against the T cells.” The research, still in the safety phase, currently includes 29 patients who received LMP-CTL therapy alone. Bollard and her team hope to eventually recruit 40 to 50 patients for this phase. Thus far, she says researchers have not seen any toxicity; and 78 percent of the patients have experienced at least partial remission; 57 percent have had complete remission.
“That’s outstanding, given that many of these patients come to us with chemo-resistant disease,” she said. For some patients the LMP-CTL therapy is not effective or only partially effective. Bollard says this may be because the tumor cells are sometimes able to evade the body’s immune system by releasing Transforming Growth Factor-beta (TGFb), which kills T cells in vivo.
In her second study, also sponsored by the NIH, Bollard is determining whether LPM-CTLs that are genetically altered to be resistant to TGFb can survive in the presence of TGFb and kill the tumor.
Among the patients receiving good news thus far is Subha Barry, a Princeton, N.J., resident who was diagnosed with Hodgkin’s lymphoma in 1997. Barry underwent multiple rounds of chemotherapy and a stem cell transplant at the University of Pennsylvania School of Medicine but was told in 2004 that she needed another stem cell transplant. Instead, she sought out Dr. Roger Strair, a Hematologist-Oncologist at the Cancer Institute of New Jersey, who referred her to Bollard.
Barry initially received LMP-CTL therapy alone and achieved a partial remission. She then received the genetically modified LMP-CTL and was told last fall that she was in full remission.
“I was one of the lucky ones,” Barry said. “They monitor me very, very closely, and essentially, I just go and live my life. I feel incredibly blessed.”