Tumor-associated oncogenes go on (phage) display

www.impactjournals.com/oncotarget 84 Oncotarget 2010; 1: 84-85 The immune system has a long-recognized ability to target select proteins produced by tumor cells. Such tumor-specific antigens may be uniquely present in cancer as a result of mutations or abnormal protein modifications. In other cases, the increased immunogenicity of structurally normal proteins is less obvious and may represent, albeit not always, elevated levels of their expression in malignant cells. Immune response to tumor-specific antigens raises two important questions: could it be selectively enhanced for a therapeutic effect, and could it be used to discover the actual antigens in order to understand the properties of the tumors and to diagnose and classify the disease? The thought-provoking report by Ionov in the current issue of this journal offers news insights into advancing both of these issues [1]. The experimental approach (See Figure) relies on the use of a phage-display library, which is first depleted of the phages that bind to control antibodies, such as the ones obtained from a healthy donor, and then is subjected to precipitation using an antibody fraction from a cancer patient. The phages enriched at this step are expected to display the peptides that are recognized by patient’s, but not control’s antibodies. The unbound phages are eliminated, while the precipitated ones could be rescued in bacteria. This sequence of steps could be repeated multiple times for further enrichment. Subsequently, the sequence of the presented peptides is determined by sequencing the enriched phages. These data are examined for homology to known human proteins. Not surprisingly, the short peptides reveal homology to numerous proteins. The picture is further complicated by an obvious fact that some epitopes may not be continuous, or may include posttranslational modification and, hence, would not be detected in a trivial homology search. The key assumption that Ionov made is that an immunogenic protein is likely to be targeted by multiple antibodies, and at least some of them would have continuous epitopes. If this is the case, one may Tumor-associated oncogenes go on (phage) display