Cancer patients develop antitumor immune responses, both humoral and cellular, against antigens expressed by their tumors. Low-throughput antigen cloning has been used to identify a number of immunogenic tumor antigens, but this process has limited utility for diagnostics or therapeutic vaccines. A novel approach to the identification of diagnostic antigens that utilizes a combination of high-throughput selection and protein-microarray-based serological detection of complex panels of antigens that are indicative of the presence of cancer, is described herein, and should lead to a great diversity of vaccine candidates. This technology exploits the immune system as a biosensor to diagnose the presence of cancer through serum testing, and the repertoire of antigen biomarkers identified can then be further employed as immunotherapeutic targets. Given the heterogeneity exhibited by tumors, there will be a higher probability of eliciting a cytotoxic antitumor immune response in cancer patients if multiple antigens that are personalized to an individual patient's patterns of autoantibody binding are used for immunotherapy.