MUC-1 Tumor Antigen Agonist Epitopes for Enhancing T-cell Responses to Human TumorsScientists at NIH have identified 7 new agonist epitopes of the MUC-1 tumor associated antigen. Compared to their native epitope counterparts, peptides reflecting these agonist epitopes have enhanced ability to generate cytotoxic T-lymphocytes (CTL), which in turn have a greater ability to kill MUC-1 expressing human tumor cells. The agonist epitopes span both the VNTR region of MUC-1 and the C-terminus region. The epitopes encompass two major MHC alleles reflecting the majority of the population.
Along with the method of use, the technology encompasses the use of these agonist epitopes in peptide- and protein-based vaccines, with dendritic cells or other antigen presenting cells, or encoding sequences in DNA, viral, bacterial, yeast, or other types of vectors, or to stimulate T-cells in vitro for adoptive immunotherapy protocols.
The MUC-1 tumor associated antigen has been shown to be overexpressed and/or underglycosylated in a wide range of human cancers. The C-terminus region of MUC-1 (MUC-1C) has been shown to be an oncogene and has been associated with a more aggressive phenotype in several different cancers.
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