NEW MOLECULAR RECEPTORS FOR DIAGNOSIS AND THERAPY OF PANCREATIC DUCTAL ADENOCARCINOMA

Abstract

\n \n \n Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with worst prognosis due to the intense desmoplastic reaction that occurs in this disease, which hinders the action of therapeutic agents and contributes to cancer progression. A possible way to develop new strategies for PDAC diagnosis and therapy is the study of the abnormal components of the tumor stroma. However, new receptors capable of detecting these components are needed.\n \n \n \n Two types of molecular receptors, monoclonal antibodies and aptamers, were developed in parallel targeting an extracellular matrix protein with potential as a PDAC marker. Antibodies were generated using mice of the DBA/1J strain, while aptamers were obtained by means of an in vitro selection method called SELEX. The analytical characteristics of the developed receptors were studied by ELISA-like assays, as well as cytochemistry on positive and negative cell lines for the protein of interest.\n \n \n \n A total of 44 potential aptamers were identified. After a first bioinformatic screening, 9 candidates were chosen for evaluating their binding affinity in vitro. Two of them showed dissociation constants in the nanomolar range. One of the aptamers also showed specific staining of cells positive for the marker protein, as did one of the generated antibody clones.\n \n \n \n The newly developed receptors have shown a great potential in the study of PDAC. However, their diagnostic and therapeutic usefulness requires a more in-depth evaluation, currently in progress.\n \n \n \n This research was funded by the Spanish Government (RTI-2018-095756-B-I00) and Principado de Asturias Government (IDI2018-000217), co-financed by FEDER funds. R.L.G. thanks the Spanish Government for a predoctoral FPU fellowship (FPU16/05670).\n