Tumor-associated antigens (delivered by DRibble vaccine) (TAA (DRibble))

Tumor-associated antigens delivered by the DRibble vaccine represent a diverse pool of immunogenic proteins, including defective ribosomal products (DRiPs), misfolded proteins, and heat shock proteins, sequestered within autophagosome-enriched microvesicles (Hu et al., 2011, J Immunother). Unlike traditional vaccines that target a single antigen, the DRibble platform captures the entire antigenic fingerprint of a tumor cell, including neoantigens and short-lived proteins that are usually degraded by the proteasome (Sanborn et al., 2013, Cancer J). These vesicles are produced by treating tumor cells with proteasome inhibitors and autophagy inducers, which causes the accumulation of ubiquitinated proteins within autophagosomes (Li et al., 2011, Cancer Res). When administered as a vaccine, these vesicles are specialized for cross-presentation by professional antigen-presenting cells, particularly Clec9A+ dendritic cells, leading to the activation of a broad repertoire of T cells (Yi et al., 2012, J Immunother). This approach is designed to overcome tumor heterogeneity and prevent immune escape by targeting multiple antigens simultaneously (Ye et al., 2014, Clin Cancer Res). Clinical investigations have primarily focused on its application in solid tumors such as non-small cell lung cancer and breast cancer (NCT00850785).

Other names

DRibblesDefective Ribosomal Products-containing blebsAutophagosome-enriched vesiclesDRP-containing blebsUbi-40 vaccine

The DRibble vaccine delivers a broad spectrum of tumor-associated antigens, including defective ribosomal products (DRiPs) and short-lived proteins, encapsulated within autophagosome-enriched vesicles. These vesicles are efficiently captured by professional antigen-presenting cells, such as dendritic cells, via receptors like CLEC9A. Once internalized, the antigens undergo cross-presentation to both CD4+ and CD8+ T cells, triggering a robust and polyvalent anti-tumor immune response (Hu et al., 2011; Li et al., 2011).