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COMPOSITIONS OF TUMOR SPECIFIC NEOANTIGENS FOR USE IN TREATING TUMOURS

机译:用于治疗肿瘤的特定肿瘤新药的组成

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.
机译:用于诱导肿瘤特异性免疫反应的方法中的两种或多种肽或多肽和佐剂,其中所述肽或多肽已通过以下方法鉴定:鉴定用于制备受试者特异性免疫原性组合物的多种新抗原肽,每种新抗原肽包含肿瘤特异性新表位,所述新抗原表位包含肿瘤特异性突变,所述方法包括:一种。通过对来自该受试者的肿瘤和正常组织样品的全基因组或全外显子组核酸测序,鉴定患有癌症的受试者的表达基因中的多个受试者特异性肿瘤突变,其中所述突变存在于受试者的癌细胞基因组中但不在受试者的正常组织中;b。其中当步骤(a)中鉴定的突变是点突变时:一世。鉴定具有步骤(a)中鉴定的突变的突变肽,其中所述突变肽包含肿瘤特异性新表位,其与I型HLA蛋白结合的亲和力大于野生型肽。 IC50小于500 nm;C。其中当步骤(a)中鉴定的突变是剪接位点,移码,通读或基因融合突变时:一世。鉴定由步骤(a)中鉴定的突变编码的突变多肽,其中所述突变多肽包含与I类HLA蛋白结合的肿瘤特异性新表位。

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