Autoantibodies as Biomarkers in Lung Cancer

Immune response manifested by annexins I and II autoantibodies occurs commonly in lung cancer and is associated with high circulating levels of IL-6 - an inflammatory cytokine. A proteomic approach using 2D PAGE, followed by Western blot analysis in which individual sera were tested for primary antibodies has led to the discovery of antiannexins I and/or II in sera from patients with lung cancer. Biomarkers have been detected in 90% of cases of lung adenocarcinoma. The CARET (Carotene and Retinol Efficacy Trial) feasibility study showed that anti- annexin antibodies could be detected in serum samples collected a year prior to clinical diagnosis of lung cancer.

Researchers at the University of Kentucky have described a fluorescent protein microarray to identify and measure multiple NSCLC-associated antibodies and showed how simultaneous measurements can be combined into a single diagnostic assay. Measurements of the five most predictive phage proteins were combined in a logistic regression model that achieved 90% sensitivity and 95% specificity in prediction of patient samples, whereas leave-one-out statistical analysis achieved 88.9% diagnostic accuracy among all 81 samples. In testing this marker set with samples from the Mayo Clinic Lung Screening Trial, the authors correctly predicted six of six prevalence cancers, 32 of 40 cancers from samples drawn 1 to 5 years before radiographic detection on incidence screening, and 49 of 56 risk-matched controls. These data indicate that antibody profiling is a promising approach that could achieve high diagnostic accuracy for NSCLC. These were licensed by 20/20 GeneSystems for development into a test for early detection of lung cancer using a combined panel of 4 biomarkers. This test can find the most common types of lung cancer and can identify risk at an early stage when intervention and treatment can improve survival chances. The test reports results using a simple risk score, generated from the panel of biomarkers, to give physicians insight on the likelihood that the patient has lung cancer. The reported result is a single numeric score with a cutoff showing a High/Low risk, relative to other persons with similar age and smoking history.

Panels of autoantibody serum assays in development by OncImmune Ltd. are unique in that they are designed to detect the first changes in proteins when cancer is developing. The assays have been optimized to display the proper epitopes in the proper orientation to bind to autologous antibodies. EarlyCDT-Lung test (OncImmune Ltd) measures a panel of 7 autoantibodies to detect the presence of lung cancer.

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