PMID- 23466067
OWN - NLM
STAT- MEDLINE
DCOM- 20131105
LR  - 20220408
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 228
IP  - 1
DP  - 2013 May
TI  - The safety of therapeutic monoclonal antibodies: implications for cardiovascular 
      disease and targeting the PCSK9 pathway.
PG  - 18-28
LID - S0021-9150(13)00106-8 [pii]
LID - 10.1016/j.atherosclerosis.2013.01.044 [doi]
AB  - 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.
CI  - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved.
FAU - Catapano, A L
AU  - Catapano AL
AD  - Department of Pharmacological and Biomolecular Sciences, University of Milan, 
      Italy; IRCCS Multimedica, Italy. Alberico.catapano@unimi.it
FAU - Papadopoulos, N
AU  - Papadopoulos N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130208
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Antibodies, Monoclonal)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
RN  - EC 3.4.21.- (Proprotein Convertases)
RN  - EC 3.4.21.- (Serine Endopeptidases)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*administration & dosage/*adverse effects
MH  - Cardiovascular Diseases/*drug therapy/immunology/metabolism
MH  - Humans
MH  - Hypercholesterolemia/*drug therapy/immunology/metabolism
MH  - Proprotein Convertase 9
MH  - Proprotein Convertases/immunology/*metabolism
MH  - Serine Endopeptidases/immunology/*metabolism
EDAT- 2013/03/08 06:00
MHDA- 2013/11/06 06:00
CRDT- 2013/03/08 06:00
PHST- 2012/10/08 00:00 [received]
PHST- 2013/01/09 00:00 [revised]
PHST- 2013/01/29 00:00 [accepted]
PHST- 2013/03/08 06:00 [entrez]
PHST- 2013/03/08 06:00 [pubmed]
PHST- 2013/11/06 06:00 [medline]
AID - S0021-9150(13)00106-8 [pii]
AID - 10.1016/j.atherosclerosis.2013.01.044 [doi]
PST - ppublish
SO  - Atherosclerosis. 2013 May;228(1):18-28. doi: 
      10.1016/j.atherosclerosis.2013.01.044. Epub 2013 Feb 8.