| 主权项 |
1. A method of inducing a tumor specific immune response in a subject in need thereof comprising administering to the subject:
(a) 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 subject-specific peptides; or (b) one or more polynucleotide encoding the 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 subject-specific peptides; wherein the subject has a tumor and said subject-specific peptides are specific to the subject's tumor, wherein each of said subject-specific peptides has a different tumor neo-epitope that is an epitope specific to the tumor of the subject, wherein each neo-epitope binds to a HLA protein of the subject with an IC50 less than 500 nM; and wherein each neo-epitope represents a tumor-specific non-silent mutation selected from the group comprising
(i) non-synonymous mutations leading to different amino acids in the protein;(ii) read-through mutations in which a stop codon is modified or deleted, leading to translation of a longer protein with a novel tumor-specific sequence at the C-terminus;(iii) splice site mutations that lead to the inclusion of an intron in the mature mRNA and thus a unique tumor-specific protein sequence;(iv) chromosomal rearrangements that give rise to a chimeric protein with tumor-specific sequences at the junction of two proteins (i.e., gene fusion);(v) frameshift mutations or deletions that lead to a new open reading frame with a novel tumor-specific protein sequence. |
