TLR ligand-peptide conjugate vaccines: toward clinical application

Abstract

Approaches to treat cancer with therapeutic vaccination have made significant progress. In order to induce efficient antitumor immunity, a vaccine should target and activate antigen-presenting cells, such as the dendritic cell, while delivering the tumor-derived antigen of choice. Conjugates of synthetic peptides and ligands of pattern-recognition receptors (PRRs) combine these features and, given their synthetic nature, can be produced under GMP conditions. Therefore, conjugation of antigenic peptides to potent PRR ligands is a promising vaccination approach for the treatment of cancer. This review focuses on the different PRR families that can be exploited for the design of conjugates and explores the results obtained so far with PRR ligands conjugated to antigen. The uptake and processing of Toll-like receptor ligand-peptide conjugates are discussed in more detail, as well as future directions that may further enhance the immunogenicity of conjugates.