Novel Two-step Immunotherapy Showed Promise for Patients with Recurrent Ovarian Cancer
A novel two-step immunotherapy approach yielded clinically beneficial responses in patients with advanced ovarian cancer, including one patient who achieved complete remission, according to data from two phase I clinical trials presented at the AACR Annual Meeting 2013, held in Washington, DC, April 6 to 10.
“This immunotherapeutic strategy has two steps—dendritic cell vaccination and adoptive T-cell therapy. This is the first time such a combination immunotherapy approach has been used for patients with ovarian cancer,” said Lana Kandalaft, PharmD, MTR, PhD, Assistant Professor and Director of Clinical Development and Operations at the Ovarian Cancer Research Center in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. “Most patients with ovarian cancer are diagnosed at an advanced stage, and many of those relapse within 2 years; most die within 5 years. Given these grim outcomes, there is definitely a vast unmet need for the development of novel, alternate therapies.”
Dendritic Cell Vaccination
According to Dr. Kandalaft, the first step of the immunotherapy approach is to preserve the patient’s tumor at the time of surgery so it can be used to manufacture a personalized vaccine that teaches the patient’s own immune system to attack the tumor.
For this protocol, Dr. Kandalaft and colleagues isolated immune cells called dendritic cells from the blood of 31 patients with recurrent, progressive, stage III and IV ovarian cancer. They then prepared the vaccine by exposing each patient’s dendritic cells to her own tumor tissue that had been collected during surgery. The first six patients were assigned to the first version of a vaccine, while the other 25 were assigned to an enhanced vaccine with an optimized platform developed at the Penn Ovarian Cancer Research Center.
Nineteen of these patients showed clinical benefit after vaccine treatment and developed an antitumor immune response. Of these 19 patients, 8 had no measurable disease at the end of the study and remained on maintenance vaccine therapy. One of the eight patients remained disease-free for 42 months following vaccine treatment.
Adoptive T-cell Therapy
Eleven patients who responded to the vaccine treatment but still had residual disease moved to the second step of the immunotherapy: adoptive T-cell therapy. At this point, the researchers removed T cells from patients’ blood, stimulated and expanded the cells in the laboratory, and then reinjected them into the patients. The team found that because the T cells had already been educated by the dendritic cell vaccine to attack the tumor cells, the adoptive T-cell transfer amplified the antitumor immune response. Of these 11 patients, 7 had stable disease and 1 had a complete response.
While vaccination therapy alone showed about a 61% clinical benefit, the combination of both therapies showed about a 75% benefit, according to Dr. Kandalaft. “We offer patients with ovarian cancer a potential therapy with minor side effects and a good quality of life,” she said. The team continues to work to improve the vaccine platform to further enhance its efficacy.
Both treatments were given in conjunction with bevacizumab (Avastin), a drug that controls blood vessel growth. Combining bevacizumab with immunotherapy makes a powerful duo, according to Dr. Kandalaft. Currently, the vaccine trial is still open to accrual to test new combinatorial strategies.
This study was funded by a National Cancer Institute Ovarian Specialized Program of Research Excellence grant, the National Institutes of Health and the Ovarian Cancer Immunotherapy Initiative.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
