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Atherosclerosis. 2013 May;228(1):18-28. doi: 10.1016/j.atherosclerosis.2013.01.044. Epub 2013 Feb 8.

The safety of therapeutic monoclonal antibodies: implications for cardiovascular disease and targeting the PCSK9 pathway.

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1
Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; IRCCS Multimedica, Italy. Alberico.catapano@unimi.it

Abstract

Monoclonal antibodies (mAbs) are established therapies for many conditions, including cancers, autoimmune conditions and infectious diseases. mAbs can offer benefits over conventional pharmacotherapy in terms of potency, dosing frequency and specificity for their target antigen. Mouse-derived antibodies were initially used in humans; however, patients often developed human anti-mouse antibodies, resulting in rapid antibody clearance (and a resulting loss of efficacy) and hypersensitivity reactions. Chimeric, humanized, and fully human antibodies were thus developed, with increasing amounts of human sequence, to reduce immunogenicity. Although generally well tolerated, mAbs may be associated with adverse events (AEs). Many AEs are target-related, and will be specific to the antibody target and the therapeutic area of use. However, off-target AEs, such as hypersensitivity reactions, are observed with many antibodies. Within the realm of cardiovascular medicine, new antibody-based therapies are under investigation to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma LDL-C levels by increasing degradation of the LDL receptor (LDLR). Therefore, inhibition of the interaction between PCSK9 and the LDLR with mAbs targeting PCSK9 has great potential for patients with hypercholesterolaemia. Early clinical phase studies suggest these mAbs are effective and well tolerated; however, further studies are required to assess their long-term safety.

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