Peptide ESL

Vaccination with synthetic long peptides (SLPs), covering viral or tumor epitopes, has shown promising results in experimental models and recently also in clinical therapeutic vaccination trials. This peptide-based vaccine platform allows covering multiple (overlapping) MHC classes I and II epitopes and therefore does not require the necessity for HLA-typing for each patient to be treated. Moreover, in contrast to short peptides, SLPs are not able to bind directly to MHC class I and their presentation to CD8+ T cells therefore requires uptake and processing by antigen-presenting cells (APCs) such as dendritic cells (DCs) before they are presented. This is advantageous, as properly activated dendritic cells (DCs) are vital for the strength of the ensuing T-cell responses. Other immune cells for example generally lack the capacity to provide adequate T cell costimulation and thus may cause tolerance. The efficacy of a particular peptide vaccine is however influenced by many parameters and its success ranges from inducing clinical efficacy to detrimental effects such as hyperreactivity and hyporesponsiveness. Mechanistic studies with peptide vaccines in different experimental models revealed that by more specific targeting, improving the uptake of SLPs, and/or activation of APCs the SLP-based vaccines generally advance leading to better clinical success.