PubMed · 16149601
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Takao Kawabe. 2005. [CA50].. https://pubmed.ncbi.nlm.nih.gov/16149601/
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To improve tumor targeting in a subset of patients, where tumor cells do not express the well-known tumor antigens widely used in immunotherapy, we have developed a novel biotechnological tool. It is useful for tumors of various origins for the identification of tumor-associated proteins, which are differentially expressed in tumor cells with respect to normal tissue, and exposed on the cell surface. For this purpose, a combination of techniques, such as "suppression subtractive hybridization" and "transmembrane trapping," was employed. In applying this novel approach to breast cancer, we identified a large panel of cDNA fragments encoding for the well-known tumor-associated surface antigens, such as erb-B2, erbB3 and the urokinase receptor and, more importantly, for several clones overexpressed in breast cancer, whose cDNA fragments match the sequences of hypothetical transmembrane proteins with unknown function. The latter may represent novel tumor-specific targets.
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.
PURPOSE: We aimed to identify the key proteins that influence the prognosis of non-small cell lung cancer (NSCLC) using protein expression profiles of previously known prognostic markers. METHODS: Thirty-one cases of Stage II NSCLC with 5-year follow-up data were selected. Tissue microarrays (TMA) and immunohistochemistry were used to make protein expression profiles of 18 previously reported immunohistochemical prognostic markers and their value in NSCLC was statistically re-evaluated by a discriminant analysis. RESULTS: For the discriminant analysis using marker protein expression profiles, we selected three significant markers, TTF-1, RCAS1 and c-MET, to evaluate each patient's 5-year survival. The requested discriminant function was V = -1.08754 x (RCAS1 score) - 0.83174 x (TTF1 score) + 0.55204 x (cMET score) + 5.46972, and V = 0 served as a cut-off point. The correctness for evaluating a patient's 5-year survival by a discriminant analysis was 87.1%. CONCLUSIONS: A discriminant analysis is thus considered to be a useful statistical method for analyzing the protein expression profiles obtained by combined TMA and immunohistochemical techniques using archival NSCLC tissues. However, the sample size and selection of the marker protein depending on the histology greatly influence the results of a NSCLC study.