Lana Kandalaft, PharmD, PhD
A two-step immunotherapy approach consisting of adoptive T-cell therapy and a dendritic cell vaccine has shown activity in a phase I advanced ovarian cancer clinical trial. The results were presented at the 2013 AACR Annual Meeting by Lana Kandalaft, PharmD, PhD, assistant professor and director of Clinical Development and Operations at the Ovarian Cancer Research Center at the Perelman School of Medicine, University of Pennsylvania, Philadelphia.
All patients had recurrent, progressive, stage III and IV ovarian cancer. Out of 31 patients treated with the vaccine, 19 (61%) showed a clinical benefit from the combination immunotherapy. Eight of the 19 patients had no measurable disease at the end of the trial but remained on maintenance vaccine therapy. One patient remains disease-free after 42 months in complete remission.
Ovarian cancer is the fifth leading cause of death from cancer among women. It remains difficult to treat, partly because it is typically diagnosed at an advanced stage, and there is a high unmet need for better, more durable treatment of advanced ovarian cancer. The 5-year survival rate for stage IV invasive epithelial ovarian cancer is approximately 18%.
The new immunotherapy requires a sample of the patient’s tumor taken at the time of surgery in order to create a personalized vaccine. Researchers isolate dendritic cells (immune cells) from the tumor sample.
Six of the patients in the trial received an initial version of the vaccine, and the subsequent 25 received an optimized version developed at the Penn Ovarian Cancer Research Center. According to Kandalaft, the team is continuing to work to improve the vaccine. As long as the tumor tissue from the patient is resected at the time of surgery in a sterile manner and preserved while the tissue is still alive using cryogenics, the vaccine can be created, according to Kandalaft.
Eleven patients in total were treated with the combination of dendritic cell vaccine and adoptive T-cell therapy. All of these patients initially received the vaccine but still had residual disease and went on to receive adoptive T-cell therapy. The patients’ T-cells were removed from peripheral blood samples, expanded in the laboratory, and then re-injected into patients. Seven of the 11 patients had stable disease and one had a complete response.
Analyses showed that because the patients’ immune systems were already primed by the dendritic cell vaccine to attack tumor cells, the subsequent adoptive Tcell transfer magnified the immune response further.
One of the current goals of the research team is to identify what was unique about the patient who achieved complete remission. “The patient had tumor infiltrating lymphocytes in her tumor tissue at the time of surgery,” said Kandalaft. Not all patients have evidence of such a spontaneous immune response in the form of immune cells that are able to infiltrate into the tumor. Other patients in the trial who had a clinical benefit also had such a spontaneous immune response.
Both the vaccine and combination immunotherapy treatments were combined with bevacizumab (Avastin).Both the vaccine and combination immunotherapy treatments were combined with bevacizumab (Avastin).
Patients tolerated the vaccination regimen well, according to the researchers. These results suggest that further development of the two-step immunotherapy regimen is promising for the treatment of patients with ovarian cancer.
“We are planning to take the dendritic vaccine into the primary setting with a clinical trial for patients who are in remission,” said Kandalaft. Treating this population of patients who are likely to have a healthier immune system compared to patients with more advanced cancer could help prevent recurrence and may provide more benefit in this setting compared to patients with advanced cancer who have already been exposed to multiple therapies.
The study was funded by the National Institutes of Health, the Ovarian Cancer Immunotherapy Initiative, and a National Cancer Institute Ovarian Specialized Program of Research Excellence grant.
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. Presented at: the AACR Annual Meeting 2013; April 6-10, 2013; Washington, DC. Abstract LB-335.