Project DTEST-CLP aims to develop innovative diagnostic test system for early detection of pathological changes during the development of cardio-metabolic disorders and cancer. This test system will be based on the detection of new biomarkers - chitinase-like proteins (CLP) YKL-39, YKL-40 and SI-CLP (Figure 1). CLP are produced by cancer cells and by key innate immune cells – macrophages. Expression of CLPs is induced in sites of inflammation and in tumors. We will use innovative approach to design antigens for the generation of anti-CLP antibodies and develop advanced detection system to measure simultaneously concentrations of all three chitinase-like proteins in human blood circulation. Novel antibodies raised against various functional domains of CLP will be examined for their ability to block pathological action of CLP in functional cellular systems.
Validation of the diagnostic value of the CLP-based detection system will be performed on the cohorts of patients with different stages of atherosclerosis, type 2 diabetes and cancer.Developed by us novel diagnostic system will be rapid, affordable and highly sensitive, and will allow early diagnostic of cardio-metabolic disorders and cancer before any clinical manifestation is detectable. Developed antibodies will serve basis for the design of innovative therapeutic strategies. The project results will have high economical and social impact by decreasing diagnostics and therapy costs and by improving the quality of patients’ life.
Figure 1. Family of mammalian chitinases and chitinase-like proteins (CLP). (A) Domain organisation of mammalian Glyco_18 domain containing proteins; (B) Critical aminoacids in the catalytic sites. The characteristic FDG sequence preceding catalytic motif is shown in shadowed box. Catalytic aminoacids are shown in bold. Complete active catalytic motifs are underlined. This research was originally published in Blood. Kzhyshkowska, J et al. Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway Blood. 2006; 107:3221-3228. © The American Society of Hematology.