Personalized Vaccine Trains Immune System to Fight Ovarian Cancer

Cancer cell (white) being attacked by immune T cells (red). Ovarian cancer may be the next cancer to be treated with a boost to the immune system. | NIH Image Gallery/ CC BY-NC 2.0

Scientists have created a personalized vaccine that boosts the immune system's response against ovarian cancer and markedly prolongs survival in ovarian cancer patients, a study published in the April 11 issue of Science Translational Medicine finds.

The results from the pilot clinical trial show the vaccine is safe and effective when combined with drugs that regulate the immune system — a combination that could offer clinicians a new tool in the fight against a deadly form of cancer that is often resistant to standard treatments.

Ovarian cancer represents a major health burden in the U.S., resulting in an estimated 22,000 cases and 14,000 deaths in 2017, according to an NIH surveillance report . This form of cancer is particularly dangerous because it usually goes undiagnosed until its later stages, when the 5-year survival rate is less than 30%.

The current standard treatment for ovarian cancer consists of a combination of surgery and chemotherapy. However, 85% of patients still relapse after receiving this regimen and are left with no other curative options, according to Lana Kandalaft, an assistant professor at the University of Pennsylvania Perelman School of Medicine and co-author of the new study.

The dire need for new treatments has pushed researchers to explore immunotherapy strategies, which harness the patient's own immune response to help kill cancer cells. Previous research demonstrated that about 55% of ovarian cancer patients have a unique immune response that is correlated with better overall survival, said Kandalaft.

"Boosting this immune response through a vaccination approach could therefore potentially increase survival in other patients," she said.

Cancer vaccines aren't a new concept — scientists have long been interested in using vaccines to train immune cells to destroy various types of tumors. However, the therapeutic potential of cancer vaccines has yet to be realized, partially because they only help immune cells recognize a single antigen — a type of molecule on the surface of tumor cells.

Building off their previous work, Kandalaft and colleagues developed a personalized vaccine that conditions immune cells to react to multiple antigens, including new genetic mutations.

The vaccine is comprised of dendritic cells, or cells that trigger immune responses, derived from a patient's own blood. After being isolated from the patient, the cells are exposed to a fluid containing purified tumor cells taken from the patient's tumor before being reinjected in vaccine form. The entire process takes five days.

"We strongly believe if we can generate an immune response earlier in the treatment process we can positively influence the prognosis of these patients and give them a survival advantage."

Janos Tanyi

The authors administered the vaccine to 25 patients with recurrent ovarian cancer who had received chemotherapy in the past and followed the patients over the course of two years. All of the patients tolerated the vaccine well, according to the study.

The research group also tested whether the vaccine would be more effective when combined with drugs that regulate the immune system. Of the 25 patients, 10 patients also received bevacizumab, an approved medication that slows the growth of new blood vessels in tumors. Another 10 patients received bevacizumab in combination with cyclophosphamide, a drug used to treat various cancers.

As the study progressed, the scientists noted the vaccination amplified the immune system's response towards tumors, an effect that was augmented in the patients who also received the immunoregulatory drugs.

"The patients who received the vaccine mounted an immune response against their own tumors," said Kandalaft. "This response was represented by an increased number of immune cells which were specific to the tumor and were able to kill tumor cells."

After one year, all of the patients who received the vaccine had survived. Furthermore, after two years the overall survival rate was much higher in the patients who received the combined treatment (78%) compared to a group of 56 patients outside the study who received bevacizumab and cyclophosphamide, but no vaccine (44%), according to Kandalaft.

The authors noted their approach comes with several limitations. Creating the vaccine requires having access to specially prepared samples of the patient's tumor. If patients don't have a tumor properly stored and preserved in the right format, they can't receive the vaccine, said Kandalaft.

Nevertheless, the findings prove that immunotherapy will play a major role in the treatment of ovarian cancer in the future, according to Janos Tanyi, an assistant professor at the University of Pennsylvania Perelman School of Medicine and co-author of the study.

The researchers plan to conduct randomized studies with more patients to better validate whether the vaccine prolongs survival. They will also investigate whether the vaccine could be administered earlier on as part of the first line of treatment.

"We strongly believe if we can generate an immune response earlier in the treatment process we can positively influence the prognosis of these patients and give them a survival advantage," Tanyi said.