Personalized ovarian cancer vaccine shows promise in trial

Delegates at a conference in the US this week are hearing about early results of a trial of a new personalized ovarian cancer vaccine that offers new hope for the large number of patients who relapse after treatment.

Three-quarters of trial patients who received the new two-step immunotherapy appeared to respond to the treatment, including one patient who achieved completed remission, say researchers from the Perelman School of Medicine at the University of Pennsylvania.

Lead author of the study, Lana Kandalaft, a research assistant professor of Obstetrics and Gynecology and director of clinical development and operations in Penn Medicine’s Ovarian Cancer Research Center, is presenting the findings on Wednesday at a Late Breaking Poster session of the AACR 2013 Annual Meeting in Washington DC.

Kandalaft says in a statement:

“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.”

In the study of 31 patients with recurrent, progressive, stage 3 and 4 ovarian cancer, she and her colleagues report that while vaccination therapy alone showed about a 61% clinical benefit, the combination of both therapies showed about a 75% benefit.

Ovarian Cancer

Ovarian cancer is often called the silent killer because it is hard to spot in the early stages so by the time it is diagnosed the chances of survival are not good compared to many other cancers. The symptoms can often be mistaken for other conditions like constipation, bloating, weight gain and more frequent urination.

Over 60% of cases are not diagnosed until the cancer has spread to the lymph nodes and other parts of the body, vastly reducing the chances of a cure.

In the United States, where it is the fifth leading cause of cancer-related deaths among women, ovarian cancer claims more than 14,000 lives a year.

“Given these grim outcomes, there is definitely a vast unmet need for the development of novel, alternate therapies,” says Kandalaft.

Dendritic Cell Vaccination

The idea of the vaccine is to use the patient’s own tumor cells to teach her immune system to attack the tumor.

First, the researchers use sterile techniques to retrieve live tumor cells while the patient undergoes surgery. The cells must be kept alive for the next stage.

Then the researchers isolate dendritic cells from the patient’s blood using a method called apheresis, similar to the process used for donating blood.

Dendritic cells are part of the immune system; they spy on potentially harmful invaders and pass on information to the soldier T cells and B cells to shape the immune system attack.

To prepare the vaccine, the researchers expose the patient’s dendritic cells to the live tumor cells collected during surgery.

They assigned the first six patients to receive the first version of the vaccine while the other 25 were assigned to an enhanced version developed using Penn Ovarian Cancer Research Center’s own optimized platform.

19 of the patients developed an anti-tumor response. Of these, 8 had no measurable disease at the end of the study and continued to receive a maintenance dose of the vaccine therapy.

One of the 8 patients remained disease-free for 42 months after vaccine treatment.

Adoptive T-Cell Therapy

he 11 patients who developed an anti-tumor response following vaccine therapy but continued to show signs of disease were then moved to the secod step: adoptive T-cell therapy.

For this step, the researchers collected immune system T-cells from the patients’ blood, stimulated and expanded them in the lab, and then reinjected them into the patients.

They then observed how because the T-cells had already been taught by the dendritic cells to attack the tumor cells, the anti-tumor response was also boosted.

They say 7 of these 11 patients, continued with stable disease and one had a complete response.

Both treatments were given with bevacizumab (Avastin), a drug that slows the growth of blood vessels that feed the tumor.

Kandalaft says bevacizumab and immunotherapy is a powerful combination.

“This is the first time such a combination immunotherapy approach has been used for patients with ovarian cancer, and we believe the results are leading us toward a completely new way to treat this disease,” she notes.

Funds from the National Cancer Institute Ovarian Specialized Program of Research Excellence, the National Institutes of Health and the Ovarian Cancer Immunotherapy Initiative helped finance the trial.

In another recent study, researchers from Cornell University and Cold Spring Harbor Laboratory suggest that ovarian cancer may arise from stem-like cells.