Tumor-associated antigens contained in DRibble vaccine (DRibble TAAs)

Tumor-associated antigens contained in DRibble vaccine represent a heterogeneous collection of proteins and peptides derived from tumor cells, specifically sequestered within double-membrane microvesicles called DRibbles (DR-containing autophagosomes). These vesicles are produced by inducing autophagy and inhibiting proteasomal degradation in cancer cells, which allows for the capture of short-lived proteins (SLiPs) and defective ribosomal products (DRiPs) that are usually rapidly degraded (Li et al., 2011, Clinical Cancer Research). As a therapeutic strategy, these antigens are designed to be captured by professional antigen-presenting cells (APCs), such as dendritic cells, which then cross-present the broad array of epitopes to both CD4+ and CD8+ T cells (Twitty et al., 2011, Journal of Immunotherapy). This multi-antigenic approach aims to overcome tumor escape mechanisms and heterogeneity by stimulating a polyvalent immune response against the malignancy. Clinical investigations, particularly in non-small cell lung cancer and other solid tumors, have focused on the ability of these autophagosome-based vaccines to enhance anti-tumor immunity when used alone or in combination with other immunotherapies (Sanborn et al., 2015, Journal for ImmunoTherapy of Cancer). The DRibble platform is unique because it preserves the post-translational modifications and chaperone proteins, such as HSP90 and calreticulin, which act as natural adjuvants to enhance the immune response (Su et al., 2015, Oncology Letters).

Other names

DRibblesDR-containing autophagosomesDefective Ribosomal Products in blebsAutophagosome-based vaccineDRP-101 antigensTumor-derived autophagosomes

Induction of polyvalent anti-tumor immunity through the cross-presentation of a broad spectrum of tumor-associated antigens by professional antigen-presenting cells to CD4+ and CD8+ T cells.