Background: Oncoantigens are oncogenic and high immunogenicity proteins specifically expressed in cancers, and are promising targets for the development of new personalized immunotherapy. Methods: To develop new immunotherapeutics for various type of cancers, we have screened HLA-restricted epitope peptides from oncoantigens through cancer genomics-based approach; 1) selection of genes/proteins specifically overexpressed in clinical solid cancers using our original gene expression profile database and tissue microarrays covering thousands of cancer tissues, 2) characterization of their function in the growth and/or invasion of cancer cells by siRNAs and transfection assays, 3) screening of the epitope peptides recognized by human HLA-restricted cytotoxic T lymphocyte (CTL) by ELISPOT assay. Results: We identified 50 oncoantigens whose overexpression is associated with poor clinical outcome of various solid cancers and that some of their 10-amino-acid epitope peptides can strongly induce antigen-specific CTLs. We are screening predictive and monitoring biomarkers for cancer vaccine therapy through genomics/proteomics approach by analyzing pattern of genomic/proteomic profiles of clinical materials including cancer tissues and serum from clinical studies using a combination of these peptides to investigate the safety, immunogenicity, and anti-tumor effect of vaccine treatment for lung cancer patients who failed standard therapy. To date, we have identified several serum candidate biomarkers. Conclusions: Current data of the cancer vaccine therapy coupled with screening of companion diagnostics warrants further clinical studies to develop more personalized and effective immunotherapy. We introduce our current progress using this systematic approach and discuss future prospective to develop personalized cancer vaccine therapy. Clinical trial information: NCT01069575