A two-step immunologic approach that includes a personalized dendritic cell vaccine for each patient followed by adoptive T-cell therapy holds promise for the treatment of recurrent ovarian cancer, according to results of two consecutive phase I studies presented at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC.1
These studies represent “the first time that such a combinatorial approach has been used for patients with ovarian cancer,” stated Lana E. Kandalaft, PharmD, PhD, MTR, Research Assistant Professor of Obstetrics and Gynecology and Director of Clinical Development, Ovarian Cancer Research Center in the Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
The strategy requires cryopreservation of the patient’s tumor at surgery so the tumor cells can be used to manufacture a personalized vaccine programmed to attack the cancer. Dendritic cells are isolated from the blood and exposed to tumor cells. Then they are administered in the body to “educate” the patient’s T cells. Dr. Kandalaft called the educated T cells “soldiers that go back into the body to fight the tumor.”
The study included 31 patients with recurrent, progressive, stage III/IV ovarian cancer. Following surgery, the personalized vaccine was created and cryopreserved. Patients had the option to get standard-of-care chemotherapy before enrolling in the trial.
The vaccine is given intranodally in the groin five times over about 3 months of therapy. Some patients went on to the next step, which was adoptive T-cell therapy with T cells collected from the blood after being primed during the vaccine process. These T cells are cryopreserved, then expanded and reinfused into the patient.
Of the 31 patients who received a personalized vaccine, 20 (64%) had clinical benefit (3 partial responses and 17 with stable disease). Of those with stable disease, six had no evidence of disease at study entry and remained disease-free at the end of the study. The longest duration without evidence of disease has been 45 months, Dr. Kandalaft said.
Eleven patients who were responders to the vaccine therapy but had residual disease moved on to the second phase of the study with adoptive T-cell therapy. Clinical benefit was observed in eight patients (about 75%), with one complete response and seven with stable disease. Side effects were minimal and limited to flu-like symptoms, she said.
Both treatments were given with bevacizumab (Avastin) to control angiogenesis. According to Dr. Kandalaft, “this is a powerful duo.” She noted that in the current cohort aspirin is being included in the mix because it opens the tumor endothelial barrier to primed vaccine T cells, according to recent work by George Coukos, MD, PhD, Director of the Penn Ovarian Cancer Research Center. Other combination strategies will be tested with the vaccine, she said.
Delayed Immune Response
“Immunotherapy is known to have a delayed response,” she explained. “In one patient, for example, multiple tumor lesions were present at baseline. At the end of the study, most of the lesions had progressed, but 6 weeks later, some lesions stabilized or regressed. The progression seen initially may be due to tumor T-cell infiltrate. Later on, these lesions do regress,” she elaborated.
The vaccination approach will also be studied in the primary setting in patients in remission after surgery. (Janos L. Tanyi, MD, PhD, Assistant Professor of Obstetrics and Gynecology at Penn Medicine, will be the primary investigator on this study.)
“The immune system is healthier at that time. We will try to boost the immune system after surgery and front-line chemotherapy to prevent recurrence. Theoretically this is the time when vaccine approaches would offer more benefit,” Dr. Kandalaft told listeners. ■
Disclosure: Dr. Kandalaft reported no potential conflicts of interest.
1. Kandalaft LE, Tanyi J, Chiang C, et al: Autologous whole-tumor antigen vaccination in combination with adoptive T cell therapy for patients with recurrent ovarian cancer. AACR Annual Meeting. Abstract LB-335. Presented April 10, 2013.
Commenting on this study, Louis M. Weiner, MD, Director of the Georgetown University Lombardi Comprehensive Cancer Center in Washington, DC, commended this study of a combinatorial immunologic approach.
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