Background: The presence of the lipoprotein(a) in plasma was first described by Kare Berg in 1963 as an LDL-like particle. Lp(a) was later identified as a risk factor for atherosclerotic diseases because of its pro-atherogenic, prothrombotic and antifibrinolytic properties. Different epidemiological studies have also suggested that Lp(a) could increase the risk of cardiovascular disease and ischemic stroke if associated with other predisposing factors such as hypercholesterolemia, hypertension, diabetes mellitus and low level of HDL. There is also experimental evidence that lipoproteins have a role in degenerative diseases and not only in atherosclerosis. Today there are few therapeutic approaches for the treatment of hyperlipidemia(a). High-affinity monoclonal antibodies are an attractive therapeutic alternative. Due to their specificity, they have the ability to selectively bind the molecule of interest, and their structure, which includes an Fc region, allows complex binding to the Fc receptor localized on the surface of monocytes and macrophages. Methods: In this study, we sought to characterize the effect of anti-Lp(A) monoclonal antibody 2E8, directed toward KIV2, in an in vitro system. The ability of the antibody to induce internalization of Lp(a) in murine macrophages (RAW cells) has been tested by an ELISA test and by microscopical evaluation of intracellular lipid accumulation. Results: The number of foam cells had increased five times compared to the non-MAb control. Conclusions: This system will allow selection of new MAbs generated against human-Lp(a), and a fine characterization of the cellular response triggered by Lp(a)-MAb complexes.
Anti-Lp(a) Antibody For Diagnosis and Therapy
PASQUETTO, MARIA VALENTINA;VISAI, LIVIA;SCOTTI, CLAUDIA
2012-01-01
Abstract
Background: The presence of the lipoprotein(a) in plasma was first described by Kare Berg in 1963 as an LDL-like particle. Lp(a) was later identified as a risk factor for atherosclerotic diseases because of its pro-atherogenic, prothrombotic and antifibrinolytic properties. Different epidemiological studies have also suggested that Lp(a) could increase the risk of cardiovascular disease and ischemic stroke if associated with other predisposing factors such as hypercholesterolemia, hypertension, diabetes mellitus and low level of HDL. There is also experimental evidence that lipoproteins have a role in degenerative diseases and not only in atherosclerosis. Today there are few therapeutic approaches for the treatment of hyperlipidemia(a). High-affinity monoclonal antibodies are an attractive therapeutic alternative. Due to their specificity, they have the ability to selectively bind the molecule of interest, and their structure, which includes an Fc region, allows complex binding to the Fc receptor localized on the surface of monocytes and macrophages. Methods: In this study, we sought to characterize the effect of anti-Lp(A) monoclonal antibody 2E8, directed toward KIV2, in an in vitro system. The ability of the antibody to induce internalization of Lp(a) in murine macrophages (RAW cells) has been tested by an ELISA test and by microscopical evaluation of intracellular lipid accumulation. Results: The number of foam cells had increased five times compared to the non-MAb control. Conclusions: This system will allow selection of new MAbs generated against human-Lp(a), and a fine characterization of the cellular response triggered by Lp(a)-MAb complexes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
