Lung cancer is the most frequent cause of cancer deaths in The Netherlands. Approximately 9.000 men and women are diagnosed with this disease every year (12,3% of the total number of cancers diagnosed) and about 8.800 people are dying of this disease annually. Non-small cell lung cancer (NSCLC) accounts for almost 80% of lung cancers. Over two-thirds of patients are diagnosed with locally advanced or metastatic disease, and their poor prognosis is due to lack of effective treatment of advanced disease. Less than 15% of the patients are surviving 5 years. The prognosis of lung cancer is better if the disease is detected early, when curative surgery and radiotherapy can be applied. Novel diagnostic and prognostic markers are urgently required. Here we propose to use a combination of genome-wide gene expression data and quantitative proteomics of membrane proteins to identify potential markers for NSCLC. Extracellular domains will be exposed on the surface of cells using a lentiviral cloning/expression system. These cells will be used to immunize proprietary mice containing a humanized single chain only antibody locus. The single chain antibodies will be cloned and analyzed in detail for their affinity and specificity towards membrane proteins exposed on the surface of NSCLC cells. Candidate antibodies will be validated for use in diagnostic and prognostic tests. Specific combinations of antibodies will possibly be further developed for therapeutic purposes. High selectivity for tumor cells will be achieved by combining the specificity of single monoclonal antibodies on multi-valent antibodies.