Definition

A vaccine composed of a lyophilized fusion protein consisting of a peptide sequence of human papillomavirus type 16 (HPV16) E7 nuclear protein fused to the Pseudomonas aeruginosa exotoxin A (PE) and an endoplasmic reticulum (ER) retention signal (KDEL) combined with the immunoadjuvant GPI-0100, a semi-synthetic dodecylamide saponin derivative, with potential immunomodulating and antineoplastic activities. Upon administration of PE/HPV16 E7/KDEL fusion protein/GPI-0100 TVGV-1, the PE moiety of the fusion protein targets and binds to CD91 (Prolow-density lipoprotein receptor-related protein 1; LRP1) expressed on a variety of cells, including antigen-presenting cells (APCs) such as dendritic cells (DCs), which facilitates the internalization, through endocytosis, of TVGV-1. Following endocytosis, this agent is proteolytically cleaved by the proteasome and the epitopes from the HPV16 E7 protein become bound to major histocompatibility complex class I (MHC-I) molecules and are presented on the DC-cell surface. This facilitates a cytotoxic T-lymphocyte (CTL)-mediated immune response against HPV16 E7 expressing-tumor cells. KDEL targets the fusion protein to the ER which increases this agent’s potential to be bound by MHC-I molecules and increases the immune response against HPV16 E7-expressing cancer cells. GPI-0100 acts as an adjuvant for vaccines to improve the immunogenicity of proteins.