PMID- 28196745
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20171127
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 485
IP  - 1
DP  - 2017 Mar 25
TI  - Development of cell-based assay for predictively evaluating the FcgammaR-mediated 
      human immune cell activation by therapeutic monoclonal antibodies.
PG  - 189-194
LID - S0006-291X(17)30318-2 [pii]
LID - 10.1016/j.bbrc.2017.02.050 [doi]
AB  - Therapeutic monoclonal antibodies (mAbs) have important roles in treatments for 
      various cancers and inflammatory diseases. Their highly target specificities 
      provide controlled safety profiles. However, therapeutic mAbs commonly pose a 
      risk of the induction of the release of cytokines, which may result in adverse 
      events including infusion reaction and cytokine release syndrome. Several 
      mechanisms are involved in the cytokine releases induced by therapeutic mAbs, and 
      the activation of immune effector cells via Fcgamma receptors (FcgammaRs) is one of the 
      putative mechanisms for most IgG-subclass mAbs. The relationship between cytokine 
      releases and mAbs' Fc functions is not fully understood. Here we developed a 
      simple reporter cell-based assay for estimating the FcgammaR-mediated activation of 
      human immune effector cells by mAbs. Our use of the cell-based assay to compare 
      Fc-engineered mAbs with different FcgammaR-activation profiles revealed that the 
      releases of inflammatory cytokines and chemokines from human peripheral blood 
      mononuclear cells (hPBMCs) induced by the mAbs were elevated by treatment with 
      Fc-engineered mAbs with higher FcgammaR-activation properties. Our results also 
      suggested the involvement of monocytic effector cells in the activation of hPBMCs 
      as sources of released cytokines and chemokines, which may lead to the immune 
      cell-mediated adverse events. Our new reporter cell assay is a promising tool for 
      evaluating and predicting the activation of human immune cells by novel 
      Fc-engineered mAbs.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Takakura, Michiko
AU  - Takakura M
AD  - AMED, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan; 
      Division of Biological Chemistry and Biologicals, National Institute of Health 
      Sciences, Tokyo 158-8501, Japan.
FAU - Tada, Minoru
AU  - Tada M
AD  - Division of Biological Chemistry and Biologicals, National Institute of Health 
      Sciences, Tokyo 158-8501, Japan. Electronic address: m-tada@nihs.go.jp.
FAU - Ishii-Watabe, Akiko
AU  - Ishii-Watabe A
AD  - Division of Biological Chemistry and Biologicals, National Institute of Health 
      Sciences, Tokyo 158-8501, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170211
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cytokines)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Antibodies, Monoclonal/*immunology
MH  - Cell Line
MH  - Cytokines/immunology
MH  - Humans
MH  - *Immunity, Cellular
MH  - Leukocytes, Mononuclear/immunology
MH  - Receptors, IgG/*immunology
OTO - NOTNLM
OT  - Adverse events
OT  - Cytokine release
OT  - Fcgamma receptors
OT  - Monoclonal antibody
EDAT- 2017/02/16 06:00
MHDA- 2017/06/07 06:00
CRDT- 2017/02/16 06:00
PHST- 2017/02/03 00:00 [received]
PHST- 2017/02/09 00:00 [accepted]
PHST- 2017/02/16 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
PHST- 2017/02/16 06:00 [entrez]
AID - S0006-291X(17)30318-2 [pii]
AID - 10.1016/j.bbrc.2017.02.050 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2017 Mar 25;485(1):189-194. doi: 
      10.1016/j.bbrc.2017.02.050. Epub 2017 Feb 11.