Promising Personalized Ovarian Cancer Vaccine Induces Immune Responses

A personalized cancer vaccine using autologous dendritic cells was well tolerated and was capable of inducing antitumor T-cell immunity in patients with recurrent ovarian cancer, according to a new small trial.

“One…form of immunotherapy that can induce a T-cell response is vaccination. Vaccines should expand the pool of available tumor-specific T cells, and they could thus provide important partners for combination immunotherapy,” wrote study authors led by Janos L. Tanyi, MD, PhD, of the University of Pennsylvania in Philadelphia. “However, the expected potential of cancer vaccines has not been realized in the clinical setting.”

The authors wrote that this could be due in part to the choice of antigens, and they tried a different approach. Their vaccine is made using autologous dendritic cells pulsed with autologous tumor lysate; the OCDC vaccine has shown promise in laboratory studies.

The new pilot study included 25 patients with recurrent advanced epithelial ovarian cancer; they had been pretreated with platinum-based regimens, but were immunotherapy-naive. The study had three cohorts: in cohort 1, five patients were treated with OCDC alone, administered every 2 weeks; in cohort 2, OCDC was combined with bevacizumab in 10 patients; and in cohort 3, the vaccine was combined with bevacizumab and low-dose cyclophosphamide. The results were published in Science Translational Medicine.

Manufacturing the vaccine was feasible in all patients. The researchers generated a total of 456 OCDC doses, and 392 were administered, at an average of about 16 doses per patient. The vaccine injections were generally well tolerated, and vaccine-related toxicities were generally transient and grade 1; no toxicities above grade 2 related to the vaccine were reported.

They found that the vaccine induced a significant T-cell response to autologous tumor antigen. There were two partial responses to the therapy, and 13 had stable disease persisting for a median of 14 months. Those patients whose on-vaccination T cells recognized autologous tumor cells or dendritic cell–presented antigen had a significantly longer progression-free survival on immunotherapy than those whose T cells did not respond. Of 11 responders to the vaccine, 8 achieved a remission inversion, and the 2-year overall survival rate of responders was 100%, compared with 25% among nonresponders.

“We show that such a personalized approach to cancer immunization is feasible, well tolerated, and safe either when given alone or when combined with intravenous bevacizumab and low-dose intravenous cyclophosphamide,” the authors wrote, adding that these results suggest further testing of the approach is warranted.