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.

“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 tumour at the time of surgery so it can be used to manufacture a personalised vaccine that teaches the patient’s own immune system to attack the tumour.

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 tumour 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 optimised platform developed at the Penn Ovarian Cancer Research Center.

Nineteen of these patients showed clinical benefit after vaccine treatment and developed an antitumour 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 tumour cells, the adoptive T- cell transfer amplified the antitumour 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.

Source: AACR