Personalized vaccine could boost survival in late-stage ovarian cancer

A clinical trial at Penn tested an ovarian cancer treatment made of dendritic cells taken from the patient’s own blood and oxidized autologous whole-tumor cell lysate. (Hazmat2)

An international team of researchers is working on a personalized vaccine to tackle late-stage ovarian cancer. During a small trial in 25 patients, they found that it was most effective when administered alongside a pair of approved cancer meds.

Only about 20% of ovarian cancers are found at the early, most treatable stage—most cases go undiagnosed until the disease has progressed, according to the American Cancer Society. If caught early, prognosis is good. But five-year survival rates drop as the cancer advances, from 90% for stage 1 to 17% for stage 4 ovarian cancer. The standard of care for advanced ovarian cancer is surgery and chemotherapy, but many patients end up relapsing and their cancer progresses.

Two researchers who are now at the Ludwig Institute for Cancer Research created a vaccine for patients with advanced, recurrent ovarian cancer. The treatment is made of dendritic cells derived from the patient’s own blood and "whole-tumor lysates," which are the contents of that patient's tumor cells. The researchers, who developed the vaccine while at the University of Pennsylvania, figured that exposing the dendritic cells to the tumor material would “train” T cells to recognize and infiltrate tumors, according to a press release.

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In a pilot study at Penn, five patients were given the vaccine alone, while two groups of 10 patients received the vaccine in combination with Roche’s Avastin (bevacizumab) or cyclophosphamide. They followed the trial participants for two years, finding the treatment elicited “robust T cell responses” against tumor cells and was well tolerated by patients. They saw that the patients who received a combo treatment had a higher average two-year survival rate than the patients on the vaccine alone.

"We've also shown that these immune responses are not just any responses, but the type that kill tumor cells, and that they correlate with better progression-free survival and better overall survival of patients," said Lana Kandalaft, an adjunct researcher at Ludwig Lausanne, in the statement. The study appears in Science Translational Medicine.

Many approaches are in the works to tackle late-stage ovarian cancer. These include a new imaging test, developed by another Penn team, that measures the amount of PARP-1 enzyme in patients with ovarian cancer to identify those who would benefit most from drugs that target PARP-1. Other players are working on T cell treatments, including the Wistar Institute, which made a modified version of CAR-T that goes after FSHR-expressing ovarian cancer cells. 

The Penn/Ludwig team is planning further studies that they hope will lead to new strategies for combination treatments in ovarian cancer. “We are looking into conducting randomized larger studies to combine vaccines with the standard of care," Kandalaft said in an interview with Science Translational Medicine. "We are also looking at bringing vaccines into the primary setting, where at the moment after a combination of chemotherapy and surgery, we have a watchful waiting period where patients don’t receive further treatment but often still recur.”