MUC1 (12-20) peptide

MUC1 (Mucin 1) protein is a type 1 transmembrane glycoprotein characterized by a large extracellular domain containing a variable number (up to 120) of 20-amino acid repeat sequences (PDTRPAPGSTAPPAHGVTSA) and a high glycosylation level on serine and threonine residues within each tandem repeat. MUC1 protein is expressed at the apical part of secretory epithelial cells and is involved in the protection of epithelial surfaces as well as intracellular signalling. However, the aberrant MUC1 overexpression along with the modification of its glycosylation pattern has been associated with several carcinomas including more than 90% of breast and pancreas cancers as wells as hematologic malignancies such as multiple myelomas and lymphomas. These hallmarks make MUC1 highly immunogenic when its expressed in tumor cells and, thus, an attractive and broadly applicable target for cancer inmunotherapy. MUC1 has indeed prompted research to develop T-cell vaccine strategies capable of inducing MUC1-specific cytotoxic T lymphocyte responses in cancer patients upon immunization with a MUC1 antigenic epitope. MUC1 epitopes presented by the HLA-A*0201 molecules are most studied and the capacity of MHC-restricted cytotoxic T lymphocytes (CTLs) to recognize MUC1-expressing tumor cells is assessed to validate the epitope. The HLA-A2-restricted MUC1 (12-20) peptide (LLLLTVLTV) derives from the leader sequence of MUC1 protein and has demonstrated the ability to induce MUC1-specific CTL responses. Nevertheless, the immunodominant region of the tandem repeat domain (amino acids 950– 958, STAPPVHNV) has been also recognized by MUC1-specific CTLs in an antigen-specific and HLA-A2-restricted fashion. The half maximal inhibitory concentrations (IC50) for the MUC1 (950– 958) peptide and the MUC1 (12-20) peptide have been determined using a competitive peptide inhibition assay and were 10.13 µg/ml and 10.89 µg/ml, respectively. Hence, these two peptides fall within the IC50 range for “medium binders”. Recently, It hase been reported that optimization of MUC1 (950– 958) peptides through specific amino acid substitution and/or aberrant glycosylation showed higher binding affinities, with IC50 ranging from 0.34 to 1.68 µg/ml. Thus, modified peptides can be considered as « high-affinity binders » which may serve for developing more efficient MUC1-specfic cancer vaccines