Tumor antigens contained in DRibbles vaccine (DRibbles)

Tumor antigens contained in DRibbles vaccine, or Defective Ribosomal Products-containing autophagosome-rich blebs, represent a complex therapeutic target consisting of a diverse array of tumor-derived proteins (Hu et al., 2011). These antigens include defective ribosomal products (DRiPs), short-lived proteins (SLiPs), and misfolded proteins that are captured within autophagosomes when the proteasomal degradation pathway is inhibited (Sanborn et al., 2017). Unlike traditional single-antigen vaccines, DRibbles provide a polyvalent source of antigens, including neoantigens and tumor-associated antigens, which are stabilized by heat shock proteins like HSP90 and HSP70 (UbiVac, 2024). These heat shock proteins act as endogenous adjuvants, promoting the maturation of dendritic cells and the efficient cross-presentation of the sequestered antigens to the adaptive immune system (Lin et al., 2019). This process triggers a broad T-cell mediated immune response capable of targeting multiple tumor epitopes, which helps to mitigate the risk of immune escape due to tumor heterogeneity (Twitty et al., 2016). Clinical development of this target is primarily represented by the vaccine DRP-101, which has been evaluated in trials for various solid malignancies, including lung and breast cancers (ClinicalTrials.gov, NCT01924182).

Other names

DRiPs-containing autophagosome-rich blebsAutophagosome-enriched tumor antigensDRP-101 antigensUbiVac-DRibbles antigens

Cross-presentation of autophagosome-sequestered tumor antigens by dendritic cells to activate a broad T-cell mediated anti-tumor immune response (Hu et al., 2011).