Immunotherapy Targeting Tumor Neoantigenic Peptides

A method for identifying tumor specific neoantigenic peptides which comprises:

• i. identifying transcripts from one or more samples isolated from a tumor driven by a transcription factor fusion and obtained from one or more subjects,
• which transcription is specifically positively regulated by said transcription factor fusion,
• which are specifically associated with the transcription-fusion tumor type, and optionally
• which are encoded by neogenes that originate from intergenic or intronic regions of the genome,
• ii. identifying open reading frame (ORF) sequences from the transcripts of step (i), optionally wherein said ORF sequences are specifically expressed in a tissue (or cell) sample from said transcription factor fusion-driven tumor.

A tumor specific neoantigenic peptide, wherein said tumor is associated with a transcription factor fusion, and wherein said peptide

• i) is encoded by a part of an (ORF) sequence from a neotranscript wherein:
• a. its expression is regulated by a transcription factor fusion as evidenced by expression in cell line wherein the expression of said transcription factor fusion is made inducible,
• b. it is specifically associated with the fusion-driven tumor type,
• c. it is are encoded by genome regions having binding motifs involved in promoter regulation such as a poly GGAA motif and/or histone marks activation, such as H3K27ac and H3K4me3 histone, located at 5 kb or less of the TSS.
• ii) is expressed at a higher level or frequency in a sample from said tumor compared to normal tissue sample.