Pilot Clinical Trial of Dendritic Cell Vaccination in Ovarian Cancer
Posted: Friday, May 18, 2018
Investigators primarily from the University of Pennsylvania found the use of oxidized whole-tumor lysate dendritic cell vaccine to be safe and effective in eliciting broad antitumor immunity, including private neoantigens, in patients with recurrent ovarian cancer. This pilot clinical trial, led by Janos L. Tanyi, MD, of the Abramson Cancer Center, University of Pennsylvania, and colleagues, suggested that vaccination may be associated with significantly prolonged survival.
The study, published in Science Translational Medicine, was based upon 392 patients who were administered the vaccine alone, in combination with bevacizumab, or bevacizumab plus low-dose intravenous cyclophosphamide until disease progression or vaccine exhaustion. When comparing responses in patients who received bevacizumab with or without cyclophosphamide, the investigators detected a significantly higher number of patients responding to the tumor antigen in the cyclophosphamide cohort (8 of 10 responders) compared with patients who did not receive cyclophosphamide.
The researchers also noted that vaccination expanded preexisting T-cell responses against neoepitopes. Vaccines targeting tumor neoepitopes could be of benefit because they may expand neoepitope-specific T cells. Expectedly, neoepitope-specific T cells could exhibit high avidity, because they presumably escape thymic selection, which depletes self-recognizing clones bearing high-affinity T-cell receptors.
“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,” noted the researchers. “The mobilization of broad antitumor immunity and neoepitope-specific T cells appears to be an important strategy.”