Cancer-testis antigens serve as an attractive target for therapeutic cancer vaccines; based on their highly-restricted expression profile and also their frequent immunogenicity in cancer patients. NY-ESO-1 is an immunogenic cancer-testis antigen that has been extensively studied as a target for immunotherapeutic cancer vaccination. Dendritic cells (DC) take up and cross-present antigen to T cells, leading to their activation and stimulation of an immune response in vivo. Cross-presentation by antigen presenting cells, such as DC, is therefore an essential element of any immunotherapeutic treatment. Several studies have described strategies to enhance antigen cross-presentation by DC. QS-21* is a naturally occurring saponin molecule which enhances T cell responses and is in current use as an immunostimulant in several clinical trials. We assessed the impact of QS-21 on the cross-presentation of three NY-ESO-1 epitopes by monocyte derived (mo)DC in vitro. In all cases, presence of QS-21 at the time of antigen delivery resulted in significantly enhanced cross-presentation. Strikingly, NY-ESO-1 epitopes could be cross-presented when delivered as a soluble protein only in the presence of QS-21, which suggests a novel role for QS-21 as a component of an immunotherapeutic vaccine.
Understanding these effects will be critical for evaluating the role of QS-21 as an immunostimulant, in addition to optimizing future immunotherapeutic cancer vaccine formulations.