sig-HELP-E6SH-kdel

sig-HELP-E6SH-kdel is an investigational therapeutic DNA vaccine developed by the Netherlands Cancer Institute (NKI-AVL) for the treatment of HPV16-positive usual vulvar intraepithelial neoplasia (uVIN). The vaccine consists of a pVAX1 plasmid encoding a fusion protein that includes a signal peptide (sig) for endoplasmic reticulum (ER) targeting, a 'HELP' cassette containing multiple CD4+ T-helper epitopes (derived from HIV Nef, tetanus toxin P30, and a synthetic pan-HLA-DR epitope), a gene-shuffled version of the HPV16 E6 oncoprotein (E6SH), and a C-terminal KDEL ER-retention signal. The shuffling of the E6 sequence is designed to eliminate its oncogenic and transforming activity while preserving immunogenic epitopes. The combination of the signal peptide and KDEL sequence enhances ER targeting and retention, which improves antigen processing and presentation by dendritic cells to prime a robust T-cell response. In clinical studies, it is administered via intradermal DNA tattoo vaccination, typically in a combination regimen with the companion vaccine sig-HELP-E7SH-kdel.

Other names

HPV16 E6 DNA vaccineHPV-16 E6 DNA vaccineHPV 16 E6 DNA vaccine