II-key/antigenic epitope hybrid peptide vaccines

摘要

Disclosed is an antigen presentation enhancing hybrid polypeptide which includes three elements. The first element is an N-terminal element consisting essentially of 4-16 residues of the mammalian li-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO: 1) and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity. The second element is a chemical structure covalently linking the N-terminal element described above to the MHC Class II-presented epitope described below. The chemical structure is a covalently joined group of atoms which when arranged in a linear fashion forms a flexible chain which extends up to the length of 20 amino acids likewise arranged in a linear fashion, the chemical structure being selected from the group consisting of: i) immunologically neutral chemical structures, ii) a MHC Class I epitope or a portion thereof, and/or iii) an antibody-recognized determinant or a portion thereof. Finally, the enhancing antigen presentation enhancing hybrid polypeptide includes a C-terminal element comprising an antigenic epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule.

主权项

1. A method for enhancing an immune response toward one or more epitopes which are associated with melanoma, the method comprising:
a) providing an Ii-Key/MHC class II hybrid comprising:
i) an N-terminal element comprising at least the LRMK [SEQ ID NO: 3]residues of the mammalian Ii key peptide;ii) a chemical structure covalently linking the N-terminal element of step i) to the MHC class II-presented epitope of element iii), the chemical structure being a covalently joined group of atoms which when arranged in a linear fashion forms a flexible chain which extends up to the length of 20 amino acids likewise arranged in linear fashion; andiii) the hybrid terminating with a C-terminal element consisting of a melanoma gp100(48-58) or gp100(45-58) associated MHC class II-presented antigenic epitope which binds to the antigenic peptide binding site of an MHC class II molecule; and b) contacting the Ii-Key/MHC class II hybrid of step a), under physiological conditions, with the following components, thereby enhancing presentation of the MHC class II-presented antigenic peptide to the T-lymphocyte:
i) an antigen-presenting cell expressing MHC class II molecules which are capable of presenting the step a) iii) antigenic epitope to a T-lymphocyte; andii) a T lymphocyte which is responsive to the MHC class II-presented epitope of element a) iii) when presented by MHC class II molecules expressed by the antigen presenting cell of step b) i).