Controlled modulation of amino acid side chain length of peptide antigens

摘要

The invention provides a method for the creation of peptide antigens comprising epitopes with at least a first modification comprising a shortened or lengthened amino acid side chain. By extension or shortening of the side chain with CH3/CH2 groups, for example, made by computer assisted modeling of the tumor antigen (peptide) bound in the MHC-I-groove, immunogenicity can be improved with minimal modification of adjacent tertiary structure, thereby avoiding cross-reactivity. Provided by the invention are methods of creating such antigens, as well as methods for therapeutic or prophylactic treatment of various conditions comprising administration of the antigens.

主权项

1. A method for preparing a composition comprising an immunogenic cytotoxic T lymphocyte (CTL) peptide antigen, the method comprising:
a) providing an immunogenic CTL peptide antigen comprising a modified E75 CTL epitope, wherein the modified E75 CTL epitope has the amino acid sequence of SEQ ID NO:2 with a α-aminobutyric acid, norvaline or norleucine at position 4, a α-aminobutyric acid, norvaline or norleucine at position 7 or an isophenylalanine at position 8 of SEQ ID NO:2; and b) formulating the peptide antigen with a pharmaceutically acceptable carrier.