Definition

An off-the-shelf (OTS) autophagosome-enriched tumor vaccine composed of dendritic cell (DC)-targeting microvesicles containing short lived proteins (SLiPs) and defective ribosomal products (DRiPs) derived from tumor cells, with potential immunostimulating and antineoplastic activities. The DriPs- and SLiPs-filled autophagosome microvesicles are made by treating two human non-small cell lung cancer (NSCLC) cell lines, UbiLT3 (non-specific histopathology) and UbiLT6 (adenocarcinoma-like) with both a proteasome inhibitor, to prevent protein degradation, and an autophagy inducer. DPV-001 contains a wide variety of NSCLC-derived TAAs, many as immunogenic altered-peptide ligands (APL), and numerous damage-associated molecular pattern molecules (DAMPs) with Toll-like receptor (TLR) 2, 3, 4, 7 and 9 agonist activities. Upon administration of allogeneic autophagosome-enriched vaccine DPV-001, the proteins in the vaccine target DCs and may stimulate the immune system to mount cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte responses against the TAAs. The TAAs are overexpressed in a variety of cancer cell types other than NSCLC. The tumor-associated SLiPS and DRiPs are highly unstable and normally degraded by tumor cell proteasomes. They are typically not processed and cross-presented by antigen-presenting cells (APCs).