A vaccine composed of a twenty seven (27) amino acid long peptide derived from histone H3 containing the amino acid substitution mutation from lysine (Lys) to methionine (Met) at position 27 (H3K27M), with potential immunoactivating and antineoplastic activities. Upon subcutaneous administration of the H3K27M long peptide vaccine, the immune system may exert a cytotoxic T-lymphocyte (CTL)-mediated immune response against H3K27M-expressing tumor cells. H3K27M is a tumor-associated antigen (TAA) specifically expressed in tumor cells but not in normal cells. H3K27M mutations, including the K27M-mutant histone-3.1 (H3.1K27M) and K27M-mutant histone-3.3 (H3.3K27M) mutations, alter the methylation and acetylation profile of histone H3 at Lys 27. Modification of H3 at Lys 27 regulates gene expression, and these mutations occur in a variety of cancer cell types.