Compositions and Methods for Identifying Tumor-Specific Neoantigens

摘要

Two or more peptides or polypeptides and an adjuvant for use in a method of inducing a tumor specific immune response, wherein the peptides or polypeptides have been identified by a method comprising:identifying a plurality of neoantigenic peptides for preparing a subject-specific immunogenic composition, each neoantigenic peptide comprising a tumor-specific neoepitope comprising a tumor-specific mutation, the method comprising:a. identifying a plurality of subject-specific tumor mutations in expressed genes of a subject having cancer by whole genome or whole exome nucleic acid sequencing of tumor and normal tissue samples from the subject, wherein the mutations are present in the genome of cancer cells of the subject but not in normal tissue from the subject;b. wherein when a mutation identified in step (a) is a point mutation:i. identifying a mutant peptide having the mutation identified in step (a), wherein said mutant peptide comprises a tumor-specific neoepitope which binds to a class I HLA protein with a greater affinity than a wild -type peptide; and has an IC50 less than 500 nm;c. wherein when a mutation identified in step (a) is a splice-site, frameshift, read-through or gene-fusion mutation:i. identifying a mutant polypeptide encoded by the mutation identified in step (a), wherein said mutant polypeptide comprises a tumor-specific neoepitope which binds to a class I HLA protein.