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Background Mutated neo-antigen-based cancer vaccines suffer from the highly complex pipeline for manufacturing personalized vaccines. The most prevalent 100 single nucleotide variations (SNVs) and InDels mutations in human cancers could be extremely useful if they would generate shared mutated neoantigens for developing off-the-shelf cancer vaccines.Methods In the present study, we performed a prediction analysis including all the mutated proteins identified in at least 5% of cancer patients. This was performed taking into consideration 70 haplotypes in the three MHC class I loci (30 HLA-A, 27 HLA-B and 13 HLA-C).Results The analysis identified >20 SNV-NeoAgs and >60 InDel-NeoAgs with a significant affinity improvement over the corresponding wt (DAI>10). These targetable shared NeoAgs are prevalently derived from PIK3CA H1047R (SNV-NeoAgs) and LARP4BT163Hfs (InDel-NeoAgs). The HLA-A*33:03 is associated with the largest number of SNV-NeoAgs and the HLA-B*58:01 is associated with the largest number of InDel-NeoAgs.Conclusions Such in-depth analysis identified the most comprehensive repertoire of shared mutated NeoAgs to date. Such shared SNV and InDel-NeoAgs would allow the development of “off-the-shelf” cancer vaccines. Indeed, according to the distribution of each HLA haplotype in at least 10% of the regional populations, therapeutic cancer vaccines based on shared mutated NeoAgs might be developed for COAD, STAD and UCEC cancers, with a global coverage, and for PAAD and UVM, with a regional coverage.