The invention provides a method of making a personalized neoplasia vaccine for a subject diagnosed as having a neoplasia which includes identifying a plurality of mutations in the neoplasia analyzing the plurality of mutations to identify a subset of at least five neo antigenic mutations predicted to encode neo antigenic peptides the neo antigenic mutations selected from the group consisting of missense mutations neoORF mutations and any combination thereof and producing based on the identified subset a personalized neoplasia vaccine.