Methods and compositions to elicit multivalent immune responses against dominant and subdominant epitopes expressed in cancer cells and tumor stroma

摘要

A nucleic acid construct encoding a polypeptide comprising one or more copies of a reactive analog cross CTL epitope PSMA288-297 (SEQ ID NO: 6) comprising 1 to 3 substitutions, wherein the reagent comprises a crossover analogue substitution I297V, and one or more copies of CTL epitope PRAME425-433 of (SEQ ID nO: 5) or a reactive analogue thereof comprising crossed 1-3 substitutions, wherein the polypeptide does not comprise a complete antigen PSMA or a antigen full PRAME, where both epitopes are encoded in a release sequence, and (i) wherein the liberation sequence of both epitopes PRAME and PSMA is located in the C-terminal of the encoded polypeptide and the the encoded polypeptide is SEQ ID NO: 4; or (ii) wherein the encoded polypeptide is SEQ ID NO: 14.