Potential target antigens for immunotherapy identified by serological expression cloning (SEREX)

Immunotherapy in cancer relies on the identification and characterization of potential target antigens that can be recognized by effector cells of the immune system. Several strategies have been developed to identify such antigens, which then can be used for immunization strategies. Serological analysis of recombinant tumor cDN expression libraries (SEREX) identifies tumor antigens based on a spontaneous humoral immune response in cancer patients. SEREX is not limited to tumor types that can be grown in cell culture nor does it depend on T-cell clones that recognize the autologous tumor. SEREX-defined antigens need to be evaluated following an algorithm of several analytical steps before they become new target antigens for active immunotherapy: expression analysis to evaluate tumor association, serological analysis with sera from tumor patients and normal individuals to prove tumor-associated immunogenicity, identification of potential peptide epitopes for CD8 and CD4 T-cells, and evaluation in T-cell assays to demonstrate their potential use as vaccine targets. We recently identified a new breast cancer differentiation antigen designated as NY-BR-1 in an autologous breast cancer SEREX screening. The different steps of further evaluation are summarized in this chapter.