Novel Two-step Immunotherapy Showed Promise for Patients With Recurrent Ovarian Cancer
April 6, 2013
- Ovarian cancer has an unmet need for novel, alternate therapies.
- Patients received a personalized vaccine developed from their own blood cells and tumor.
WASHINGTON, D.C. — 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, D.C., April 6-10.
“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, Pharm.D., M.T.R., Ph.D., 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 two years; most die within five years. Given these grim outcomes, there is definitely a vast unmet need for the development of novel, alternate therapies.”
According to 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, Kandalaft and colleagues isolated immune cells called dendritic cells from the blood of 31 patients with recurrent, progressive, stage 3 and 4 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, eight had no measurable disease at the end of the study and remained on maintenance vaccine therapy. One patient of the eight patients remained disease-free for 42 months following vaccine treatment.
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 immune cells called 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, seven had stable disease and one had a complete response.
While vaccination therapy alone showed about a 61 percent clinical benefit, the combination of both therapies showed about a 75 percent benefit, according to 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, a drug that controls blood vessel growth. Combining bevacizumab with immunotherapy makes a powerful duo, according to 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.
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About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit www.AACR.org
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