Washington, DC—A 2-step immunotherapy approach holds promise for women with advanced recurrent ovarian cancer, a disease that has limited therapeutic options. The 2 steps entail a personalized dendritic-cell vaccine, followed by adoptive T-cell therapy. In an early study reported at the 2013 American Association for Cancer Research (AACR) annual meeting, almost 66% of patients derived clinical benefit from the vaccine alone, and the use of both therapies achieved approximately a 75% benefit.
More than 60% of ovarian cancer cases are diagnosed after the disease has spread to the lymph nodes and/or to other distant sites. Ovarian cancer that responds to initial treatment typically relapses, and the prognosis is poor. There is an unmet need for novel, alternative therapies for advanced ovarian cancer.
“This is the first time that a combination immunotherapy approach has been used for patients with ovarian cancer, and we believe the results are leading us toward a completely new way to treat this disease,” stated Lana Kandalaft, PharmD, PhD, MTR, Director of Translational and Clinical Operations, Ovarian Cancer Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia.
“Our 2-step approach harnesses the immune system to create T cells that are soldiers that go back into the body to fight the cancer,” Dr Kandalaft added.
In the first phase of the study, 31 patients with advanced, recurrent stage III or IV ovarian cancer underwent surgery and chemotherapy. During surgery, patients’ tumor cells were cryopreserved to create personalized vaccines made by exposing each patient’s dendritic cells to tumor tissue. After chemotherapy, patients were vaccinated via intranodal injection into the groin several times over a period of approximately 3 months. Of the 31 patients who entered in the first phase, 20 (61%) had stable disease or better.
Of the 20 patients who responded to the vaccine, 11 continued to the second phase of adoptive T-cell therapy. T cells that had been primed by the vaccine to attack tumor cells were collected from the patients’ blood and stimulated and expanded in the laboratory; these T cells were then reinfused into the patients. Seven patients treated with adoptive T-cell therapy achieved stable disease and 1 had a complete response, for a clinical benefit rate of approximately 75%.
Dr Kandalaft said that 1 of the patients who had both treatments was cancer-free for 45 months at the time of the AACR meeting.
She pointed out that, as with other vaccines, immunotherapy has a delayed response. At baseline, there were multiple cancer sites and most had progressed by the end of the study. But by 6 weeks later, lesions were stabilized or were regressing.
“Initially, you may see progression, but this could be due to tumor infiltrate and, later on, these lesions may regress,” Dr Kandalaft said. The therapy has minor side effects, according to Dr Kandalaft.
Both treatments were given along with bevacizumab (Avastin) to control blood vessel growth. “This is a powerful duo—the vaccine plus bevacizumab. The trial is open to accrual, and we will test other combinatorial strategies,” she stated.
